Mac-1-SAP References

Mac-1-SAP mouse/human (Cat. #IT-06), Mac-1-SAP rat (Cat. #IT-33)

52 entries found for : Mac-1-SAP

Prenatal exposure to valproic acid causes allodynia associated with spinal microglial activation

Imado E, Sun S, Abawa AR, Tahara T, Kochi T, Huynh TNB, Asano S, Hasebe S, Nakamura Y, Hisaoka-Nakashima K, Kotake Y, Irifune M, Tsuga K, Takuma K, Morioka N, Kiguchi N, Ago Y (2022) Prenatal exposure to valproic acid causes allodynia associated with spinal microglial activation. Neurochem Int 160:105415. doi: 10.1016/j.neuint.2022.105415

Objective: To further understand the mechanism underlying sensory phenotypes in autism spectrum disorder (ASD).

Summary: The authors investigated the age-dependent tactile sensitivity in an animal model of ASD induced by prenatal exposure to valproic acid and subsequently assessed the involvement of microglia in the spinal cord in pain processing.

Usage: To deplete microglia in the spinal cord, Mac-1-SAP (11.2 μg/5.5 μl) was injected intrathecally at the level of L4–L5 in adult (8-week-old) mice.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Female-specific mechanisms of nociplastic pain in murine model

Hankerd K (2021) Female-specific mechanisms of nociplastic pain in murine model. The University of Texas Medical Branch at Galveston, Dept Neuroscience Thesis.

Objective: To study nociplastic pain the authors developed a murine model in which postinjury thermal stimulation of injured area triggers the transition to a nociplastic pain state more readily in females.

Summary: Postinjury stimulation of an injured area triggers the transition from transient pain to nociplastic pain, females are more susceptible to this transition, and allyl isothiocyanate -sensitive afferents at the previously injured area maintain the nociplastic pain state in a female gonadal hormone-dependent manner.

Usage: Intrathecal injection of Mac-1-SAP (IT-06) 8.85 mM in mice.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

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Role of microglia and astrocytes in spinal cord injury induced neuropathic pain

Miranpuri GS, Bali P, Nguyen J, Kim JJ, Modgil S, Mehra P, Buttar S, Brown G, Yutuc N, Singh H, Wood A, Singh J, Anand A (2021) Role of microglia and astrocytes in spinal cord injury induced neuropathic pain. Ann Neurosci 28(3-4):219-228. doi: 10.1177/09727531211046367

Summary: Given the severity and incapacitating effects of spinal cord injury neuropathic pain (SCINP), it is imperative to study the pathways involved and find new therapeutic targets in coordination with stem cell research, and to develop a new gold-standard in SCINP treatment. Chronic inflammation by microglia, when targeted with Mac-1-SAP, helps in pain reversal.

Related Products: Mac-1-SAP rat (Cat. #IT-33)

Can Src protein tyrosine kinase inhibitors be combined with opioid analgesics? Src and opioid-induced tolerance, hyperalgesia and addiction

Li Y, Bao Y, Zheng H, Qin Y, Hua B (2021) Can Src protein tyrosine kinase inhibitors be combined with opioid analgesics? Src and opioid-induced tolerance, hyperalgesia and addiction. Biomed Pharmacother 139:111653. doi: 10.1016/j.biopha.2021.111653

Summary: In this review the authors discuss the important role Src protein tyrosine kinase plays in the adverse consequences of clinical application of opioids

Usage: Intrathecal injection of Mac-1-SAP depletes microglial cells in the spinal dorsal horn and alleviates the loss of anti-nociception of morphine and prevents the decrease in morphine potency. This demonstrates that spinal microglial cells are necessary for morphine tolerance (15 µg; Leduc-Pessah et al., 2017).

See: Leduc-Pessah H et al. Site-Specific Regulation of P2X7 Receptor Function in Microglia Gates Morphine Analgesic Tolerance. J Neurosci 37:10154-10172, 2017.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Specific depletion of resident microglia in the early stage of stroke reduces cerebral ischemic damage

Li T, Zhao J, Xie W, Yuan W, Guo J, Pang S, Gan WB, Gómez-Nicola D, Zhang S (2021) Specific depletion of resident microglia in the early stage of stroke reduces cerebral ischemic damage. J Neuroinflammation 18(1):81. doi: 10.1186/s12974-021-02127-w

Summary: The role of activated microglia during the development of ischemia remains controversial. The authors investigate the function of reactive microglia in the early stage of ischemic stroke. The results showed that specific depletion of microglia resulted in a significant decrease in ischemic infarct volume and improved performance in motor ability 3 days after stroke.

Usage: Mac-1-SAP is used to specifically eliminate microglia. Hippocampal slices from mouse were incubated with 13-nM Mac-1-SAP for 3 to 7 days.

See: Montero M et al. Immunotoxic depletion of microglia in mouse hippocampal slice cultures enhances ischemia-like neurodegeneration. Brain Res 1291:140-152, 2009.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Neuroimmune interactions and osteoarthritis pain: focus on macrophages

Geraghty T, Winter DR, Miller RJ, Miller RE, Malfait AM (2021) Neuroimmune interactions and osteoarthritis pain: focus on macrophages. Pain Rep 6(1):e892. doi: 10.1097/PR9.0000000000000892

Summary: The contribution of macrophages to osteoarthritis (OA) joint damage has garnered much attention in recent years. The authors discuss how macrophages participate in the initiation and maintenance of pain in OA and provide a review of preclinical models of OA.

Usage: Using the rat monoiodoacetate-induced (MIA) model of advanced knee OA, increased microglia were observed in the ipsilateral and contralateral dorsal horn by day 7; specific ablation of spinal microglia through intrathecal injections of Mac-1-SAP (15 mcg per intrathecal injection on days 0, 1, and 2), attenuated mechanical allodynia by days 5 and 7 after MIA.

See: Mousseau M et al. Microglial pannexin-1 channel activation is a spinal determinant of joint pain. Sci Adv 4:1-12, 2018.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain

Andriessen AS, Donnelly CR, Ji RR (2021) Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain. Pain Rep 6(1):e867. doi: 10.1097/PR9.0000000000000867

Summary: Current pharmacotherapies available for bone cancer pain are insufficient to provide safe and efficacious pain relief. The authors discuss the mechanisms used by cancer cells within the bone tumor microenvironment (TME) to drive bone cancer pain.

Usage: Microglial ablation using Mac-1-SAP (15 μg in 8.8 μl i.t.) and Saporin control (Cat. #PR-01, 8.8 μg in 8.8 μl), is sufficient to attenuate nerve injury-induced pain in male, but not female mice.

See: Sorge R et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 18:1081-1083, 2015.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)

Spinal microglia-neuron interactions in chronic pain.

Ho IHT, Chan MTV, Wu WKK, Liu X (2020) Spinal microglia-neuron interactions in chronic pain. J Leukoc Biol 108:1575-1592. doi: 10.1002/JLB.3MR0520-695R

Summary: Spinal microglial activation is initiated shortly and persisted for more than 3 mo after partial sciatic nerve ligation. Intrathecal injection of Mac1-SAP, a saporin-conjugated anti-CD11b antibody to deplete microglia, abolished cold and mechanical allodynia for 2–12 wk after injury,92 supporting the role of activated microglia for chronic pain maintenance.

Related Products: Mac-1-SAP rat (Cat. #IT-33)

See Also:

Inflammatory macrophages facilitate mechanical stress-induced osteogenesis.

Zhang F, Huan L, Xu T, Li G, Zheng B, Zhao H, Guo Y, Shi J, Sun J, Chen A (2020) Inflammatory macrophages facilitate mechanical stress-induced osteogenesis. Aging (Albany NY) 12(4):3617-3625. doi: 10.18632/aging.102833

Summary: In a mouse model of distraction osteogenesis (DO), there was significant increase in macrophages in the regeneration area. This suggests that targeting inflammatory macrophages may help to improve clinical bone repair.

Usage: For saporin-mediated depletion of macrophages, DO-surgery-treated mice received an intraventricular (iv) injection of either Mac-1-SAP or Rat IgG-SAP (20µg) once every 3 days.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Rat IgG-SAP (Cat. #IT-17)

Systems pathology of neuropathic pain and fibromyalgia.

Ueda H (2019) Systems pathology of neuropathic pain and fibromyalgia. Biol Pharm Bull 42(11):1773-1782. doi: 10.1248/bpb.b19-00535 Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Maintenance mechanism of nociplastic pain in males

McDonough KE, Hankerd KM, La J-H, Chung JM (2019) Maintenance mechanism of nociplastic pain in males. Neuroscience 2019 Abstracts 218.22. Society for Neuroscience, Chicago, IL.

Summary: Recently, the International Association for the Study of Pain defined a third form of pain: nociplastic pain. A key mechanism of nociplastic pain is central sensitization (CS) persistently maintained in the absence of an underlying persistent injury. We developed a novel mouse model of nociplastic pain, which uses hindpaw capsaicin injection as a transient injury, followed by innocuous vibration stimulation, making CS persist beyond the normal resolution time. Our lab has previously shown that the normally resolving transient CS by capsaicin is maintained by ongoing nerve activity at the injury site in female mice. We preliminarily found that the persistent CS in our male nociplastic pain model is maintained by different mechanisms. Based on the literature that spinal microglia and their inflammatory mediators play a key role in other models of chronic pain, specifically in males, we hypothesize that nociplastic pain in males is due to CS maintained by activated microglia and subsequent release of inflammatory mediators such as prostaglandins generated through the cyclooxygenase (COX) pathway. To test this hypothesis, spinal microglia and COX were inhibited by intrathecally injecting the microglia-targeting toxin Mac-1-saporin or the COX inhibitor indomethacin, respectively, following establishment of a nociplastic pain state. Secondary mechanical hypersensitivity, a behavioral biomarker of CS, was mitigated by intrathecal Mac-1-saporin, whereas intrathecal indomethacin had no effect. Our results suggest that spinal microglia maintain persistent CS driving nociplastic pain in males. However, prostaglandins generated through the COX pathway do not seem to be the main inflammatory mediator involved in the maintenance of this CS.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Contribution of microglial reaction to increased nociceptive responses in high-fat-diet (HFD)-induced obesity in male mice.

Liang YJ, Feng SY, Qi YP, Li K, Jin ZR, Jing HB, Liu LY, Cai J, Xing GG, Fu KY. (2019) Contribution of microglial reaction to increased nociceptive responses in high-fat-diet (HFD)-induced obesity in male mice. Brain Behav Immun 80:777-792. doi: 10.1016/j.bbi.2019.05.026 Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Inflammatory macrophages in the sciatic nerves facilitate neuropathic pain associated with type 2 diabetes mellitus.

Saika F, Kiguchi N, Matsuzaki S, Kobayashi D, Kishioka S (2019) Inflammatory macrophages in the sciatic nerves facilitate neuropathic pain associated with type 2 diabetes mellitus. J Pharmacol Exp Ther 368(3):535-544. doi: 10.1124/jpet.118.252668

Objective: To determine whether inflammatory macrophages contribute to neuropathic pain associated with type 2 diabetes-mellitus (T2DM).

Summary: Inhibitory agents for macrophage-driven neuroinflammation could be potential candidates for novel pharmacotherapy against intractable neuropathic pain.

Usage: Injections of Mac-1-SAP or unconjugated Saporin (10 μl) were administered 3 times every 2 days. Perineural administration of Mac-1-SAP improved high-fat diet (HFD)-induced mechanical allodynia and the accumulation of F4/80+ macrophages and the upregulation of inflammatory mediators in the SCN after HFD-feeding.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)

Involvement of lysophosphatidic acid-induced astrocyte activation underlying the maintenance of partial sciatic nerve injury-induced neuropathic pain

Ueda H, Neyama H, Nagai J, Matsushita Y, Tsukahara T, Tsukahara R (2018) Involvement of lysophosphatidic acid-induced astrocyte activation underlying the maintenance of partial sciatic nerve injury-induced neuropathic pain. Pain 159:2170-2178. doi: 10.1097/j.pain.0000000000001316 Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Reduced microglial activity and enhanced glutamate transmission in the basolateral amygdala in early CNS autoimmunity

Acharjee S, Verbeek M, Gomez CD, Bisht K, Lee B, Benoit L, Sharkey KA, Benediktsson A, Tremblay M-E, Pittman QJ (2018) Reduced microglial activity and enhanced glutamate transmission in the basolateral amygdala in early CNS autoimmunity. J Neurosci 38:9019-9033. doi: 10.1523/JNEUROSCI.0398-18.2018

Objective: To identify CNS changes associated with behaviors in multiple sclerosis (MS) patients.

Summary: The data from this study reveal increased synaptic activity and spine density in early stages of experimental autoimmune encephalomyelitis (an animal model of MS) in the basolateral amygdala.

Usage: Mac-1-SAP mouse/human or Rat-IgG-SAP (control) was injected unilaterally in the BLA (1 ug/1 ul).

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Rat IgG-SAP (Cat. #IT-17)

Microglial pannexin-1 channel activation is a spinal determinant of joint pain

Mousseau M, Burma NE, Lee KY, Leduc-Pessah H, Kwok CHT, Reid AR, O’Brien M, Sagalajev B, Stratton JA, Patrick N, Stemkowski PL, Biernaskie J, Zamponi GW, Salo P, McDougall JJ, Prescott SA, Matyas JR, Trang T (2018) Microglial pannexin-1 channel activation is a spinal determinant of joint pain. Sci Adv 4:1-12. doi: 10.1126/sciadv.aas9846

Objective: To identify therapeutic targets for alleviating mechnical allodynia, a sign/symptom of arthritis.

Summary: The pannexin-1 (Panx1) channel is validated as a target; blockade of P2X7 receptors or ablation of spinal microglia prevented and reversed mechanical allodynia.

Usage: Mac-1-SAP and unconjugated Saporin (15 mg per intrathecal injection on days 0, 1, and 2). The specific depletion of spinal lumbar microglia attenuated the development of MIA-induced hypersensitivity indicating that spinal microglia causally contribute to the development of mechanical allodynia. By contrast, intrathecal injection of Control (unconjugated Saporin) did not alter the development of MIA-induced mechanical allodynia.

Related Products: Mac-1-SAP rat (Cat. #IT-33), Saporin (Cat. #PR-01)

The critical role of IL-10 in the antineuroinflammatory and antioxidative effects of Rheum tanguticum on activated microglia

Meng J, Ni J, Wu Z, Jiang M, Zhu A, Qing H, Nakanishi H (2018) The critical role of IL-10 in the antineuroinflammatory and antioxidative effects of Rheum tanguticum on activated microglia. Oxid Med Cell Longev 2018:12. doi: 10.1155/2018/1083596

Objective: To investigate anti-inflammatory and antioxidative effects of a traditional Tibetan medicine (Rheum tanguticum; RT) on activated microglia.

Summary: RT may be useful for the pharmacological intervention against excessive inflammatory and oxidative responses associated with AD by inducing the production of IL-10 by microglia.

Usage: Mac-1-SAP (Cat. #IT-06, 1.3nM) was applied to hippocampal slice cultures 24 h prior to stimulation with chromogranin A or pancreastatin.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Early CALP2 expression and microglial activation are potential inducers of spinal IL-6 upregulation and bilateral pain following motor nerve injury

Chen SX, Wang SK, Yao PW, Liao GJ, Na XD, Li YY, Zeng WA, Liu XG, Zang Y (2018) Early CALP2 expression and microglial activation are potential inducers of spinal IL-6 upregulation and bilateral pain following motor nerve injury. J Neurochem 145:154-169. doi: 10.1111/jnc.14317 Related Products: Mac-1-SAP rat (Cat. #IT-33)

Targeting macrophage and microglia activation with colony stimulating factor 1 receptor inhibitor is an effective strategy to treat injury-triggered neuropathic pain

Lee S, Shi XQ, Fan A, West B, Zhang J (2018) Targeting macrophage and microglia activation with colony stimulating factor 1 receptor inhibitor is an effective strategy to treat injury-triggered neuropathic pain. Mol Pain 14:1744806918764979. doi: 10.1177/1744806918764979

Summary: Depletion of spinal microglia with Mac-1-SAP was able to prevent and reverse neuropathic pain behavior.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Site-specific regulation of P2X7 receptor function in microglia gates morphine analgesic tolerance.

Leduc-Pessah H, Weilinger N, Fan C, Burma N, Thompson R, Trang T (2017) Site-specific regulation of P2X7 receptor function in microglia gates morphine analgesic tolerance. J Neurosci 37:10154-10172.. doi: 10.1523/JNEUROSCI.0852-17.2017

Summary: By selectively ablating microglia in the spinal cord using a Mac-1-SAP the authors demonstrate a causal role for microglia in the development, but not maintenance, of morphine tolerance in male rats.

Usage: Mac-1-SAP or unconjugated Saporin control (15 μg) was administered by intrathecal injection.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)

T-cell mediation of pregnancy analgesia affecting chronic pain in mice.

Rosen S, Ham B, Drouin S, Boachie N, Chabot-Dore A, Austin J, Diatchenko L, Mogil J (2017) T-cell mediation of pregnancy analgesia affecting chronic pain in mice. J Neurosci 37:9819-9827.. doi: 10.1523/JNEUROSCI.2053-17.2017

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Spinal microglia are required for long-term maintenance of neuropathic pain

Echeverry S, Shi XQ, Yang M, Huang H, Wu Y, Lorenzo L-E, Perez-Sanchez J, Bonin RP, De Koninck Y, Zhang J (2017) Spinal microglia are required for long-term maintenance of neuropathic pain. Pain 158:1792-1801.. doi: 10.1097/j.pain.0000000000000982

Summary: Selective depletion of spinal microglia in male rats with the targeted immunotoxin Mac-1-SAP and blockade of brain derived neurotrophic factor–TrkB signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost completely reversed pain hypersensitivity.  To selectively deplete microglia in the spinal cord, Mac-1-SAP was injected intrathecally.  In each group, rats received either an intrathecal injection of 12 mg/7 mL of Mac-1-SAP (n = 6-8) or equal volume of 0.9% saline (n 5 6) or the inactive unconjugated toxin, Saporin (n = 6).)

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)

Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents

Burma NE, Bonin RP, Leduc-Pessah H, Baimel C, Cairncross ZF, Mousseau M, Shankara JV, Stemkowski PL, Baimoukhametova D, Bains JS, Antle MC, Zamponi GW, Cahill CM, Borgland SL, De Koninck Y, Trang T (2017) Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents. Nat Med 23:355-360.. doi: 10.1038/nm.4281

Summary: The authors investigated the mechanisms underlying opiate withdrawal in rat. Depletion of spinal lumbar microglia by intrathecal injections of Mac-1–SAP (Cat. #IT-33; 20 mcg) decreased withdrawal behaviors and attenuated the severity of withdrawal without affecting morphine antinociception. Unconjugated Saporin (Cat. #PR-01; 20 mcg) was used as control and had no effect on spinal CD11b immunoreactivity or naloxone-induced morphine withdrawal.

Related Products: Mac-1-SAP rat (Cat. #IT-33), Saporin (Cat. #PR-01)

Dynamics of spinal microglia repopulation following an acute depletion.

Yao Y, Echeverry S, Shi X, Yang M, Yang Q, Wang G, Chambon J, Wu Y, Fu K, De Koninck Y, Zhang J (2016) Dynamics of spinal microglia repopulation following an acute depletion. Sci Rep 6:22839. doi: 10.1038/srep22839

Summary: This study confirms that similar to microglia in the brain, spinal microglia can repopulate rapidly following elimination, which is driven essentially by a self-renewal process. To deplete microglia in spinal cords, Mac-1-SAP (Cat. #IT-06) was injected i.t. (7 μl, 1.6  μg/μl) at the level of L4-L5 in mouse. The results support the concept that microglia repopulation, whether in the brain or in the spinal cord, is the consequence of onsite resident microglia proliferation. Newly generated microglia are fully functional and are able to respond to peripheral nerve injury and contribute to the development of neuropathic pain.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Macrophages are needed in the progression of tuberculosis into lung cancer.

Li J, Pan Y, Zhang B, Chen Q (2015) Macrophages are needed in the progression of tuberculosis into lung cancer. Tumour Biol 36:6063-6066. doi: 10.1007/s13277-015-3283-8

Summary: Approximately 30% of lung carcinomas also have tuberculosis lesions. The authors investigated the potential link between inflammatory processes and cancer in the lung. Mice with established tuberculosis infections received weekly 20 μg tail vein injections of Mac-1-SAP (Cat. #IT-06) in order to eliminate macrophages. Six months later the mice receiving Mac-1-SAP had a significantly lower incidence of lung carcinoma than control animals.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Different immune cells mediate mechanical pain hypersensitivity in male and female mice.

Sorge R, Mapplebeck J, Rosen S, Beggs S, Taves S, Alexander J, Martin L, Austin J, Sotocinal S, Chen D, Yang M, Shi X, Huang H, Pillon N, Bilan P, Tu Y, Klip A, Ji R, Zhang J, Salter M, Mogil J (2015) Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 18:1081-1083. doi: 10.1038/nn.4053

Summary: A large and rapidly increasing body of evidence indicates that microglia-to-neuron signaling is essential for chronic pain hypersensitivity. Using multiple approaches, the authors found that microglia are not required for mechanical pain hypersensitivity in female mice; female mice achieved similar levels of pain hypersensitivity using adaptive immune cells, likely T lymphocytes. This sexual dimorphism suggests that male mice cannot be used as proxies for females in pain research. Mac-1-SAP mouse/human toxin (Cat. #IT-06, 15 μg in 8.8 μl) and Saporin control (Cat. #PR-01, 8.8 μg in 8.8 μl) were administered via i.t. injection. The topic of immune system involvement in chronic pain pathophysiology is one of the most active in the pain field; that this sex difference has not been observed until now is very surprising indeed. An important implication of the current findings is that distinct strategies targeting neuroimmune signaling might be required for the treatment of chronic pain in men versus women.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)

Inflammatory macrophages promotes development of diabetic encephalopathy.

Wang B, Miao Y, Zhao Z, Zhong Y (2015) Inflammatory macrophages promotes development of diabetic encephalopathy. Cell Physiol Biochem 36:1142-1150. doi: 10.1159/000430285

Summary: Diabetes can cause neuroinflammation leading to dementia. Diabetes was induced in mice by injection of streptozotocin (STZ). In order to investigate the role of inflammatory macrophages in the development of diabetic encephalopathy, the authors used twice weekly 20-μg IP injections of Mac-1-SAP (Cat. #IT-06). Mice receiving Mac-1-SAP had significantly reduced numbers of inflammatory macrophages in the brain, and also reduced responses to STZ injection.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Mesenchymal stem cells recruit macrophages to alleviate experimental colitis through TGFβ1

Liu W, Zhang S, Gu S, Sang L, Dai C (2015) Mesenchymal stem cells recruit macrophages to alleviate experimental colitis through TGFβ1. Cell Physiol Biochem 35:858-865. doi: 10.1159/000369743

Usage: For in vivo depletion of macrophages, mice received i.v. injection of Mac-1-SAP 20 µg, twice per week.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Development of morphine analgesic tolerance is modulated by spinal P2X7 receptors

Leduc-Pessah HL, Weilinger N, Fan C, Thompson R, Trang T (2014) Development of morphine analgesic tolerance is modulated by spinal P2X7 receptors. Neuroscience 2014 Abstracts 327.08. Society for Neuroscience, Washington, DC.

Summary: Growing evidence suggests that microglia, which are immune cells in the central nervous system, are causally involved in the development of opioid analgesic tolerance. Here, we investigated the importance of spinal microglial ATP-gated P2X7 receptors (P2X7Rs) in morphine tolerance. In adult male Sprague Dawley rats, we found that seven days of systemic morphine treatment resulted in a progressive decline in morphine anti-nociception and a loss in analgesic potency, the two key features of analgesic tolerance. The development of morphine tolerance correlated with an increase in spinal Iba-1 expression, a marker indicative of microglial activation. To assess whether spinal microglia are required for morphine tolerance, we depleted microglia in the spinal cord of morphine treated rats using intrathecal injections of a saporin-conjugated antibody to Mac1 (Mac1-saporin). We found that Mac1-saporin attenuated the decline in morphine anti-nociception in rats that received chronic morphine treatment. In contrast, intervention with Mac1-saporin failed to restore morphine analgesia in rats with established tolerance. Thus, spinal microglia are causally involved in the development, but they are not required for the ongoing expression, of morphine tolerance. In addition, we found that P2X7R protein expression was markedly increased in the spinal cord of morphine tolerant animals. Pharmacological blockade of P2X7Rs with the selective antagonist A740003 attenuated the development of tolerance but did not reverse established tolerance. In BV2 microglial cells, repeated morphine treatment increased total P2X7R protein expression, an effect recapitulated by the mu-opioid receptor agonist DAMGO, and suppressed by the mu-receptor antagonist, CTAP. The morphine-induced increase in P2X7R protein expression was concomitant with a potentiation of BzATP evoked P2X7R calcium responses and inward current. Collectively, our findings suggest that spinal microglia are causally involved in the development, but not expression, of morphine analgesic tolerance. We also determined that the expression and function of P2X7R in microglia are critically modulated by mu-opioid receptors.

Related Products: Mac-1-SAP rat (Cat. #IT-33)

Activated macrophages create lineage-specific microenvironments for pancreatic acinar- and β-cell regeneration in mice.

Criscimanna A, Coudriet G, Gittes G, Piganelli J, Esni F (2014) Activated macrophages create lineage-specific microenvironments for pancreatic acinar- and β-cell regeneration in mice. Gastroenterology 147:1106-1118.e1111. doi: 10.1053/j.gastro.2014.08.008

Summary: In response to tissue damage or infection, monocytes are recruited to the injured area and differentiate into macrophages. These macrophages can perform different functions depending on the tissue type. The specific differentiation macrophages undergo in response to their environment is called polarization. The authors used a mouse pancreatic lesion model to examine the polarization of macrophages into the two distinct states known, M1 and M2. Mice received 20 μg of Mac-1-SAP mouse (Cat. #IT-06) in a tail vein injection following a pancreatic lesion, and were sacrificed on various days post-injection in order to evaluate macrophage presence at different response stages. The results demonstrate that various aspects of macrophage polarization are required for pancreatic regeneration.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Microglial VPAC1R mediates a novel mechanism of neuroimmune-modulation of hippocampal precursor cells via IL-4 release.

Nunan R, Sivasathiaseelan H, Khan D, Zaben M, Gray W (2014) Microglial VPAC1R mediates a novel mechanism of neuroimmune-modulation of hippocampal precursor cells via IL-4 release. Glia 62:1313-1327. doi: 10.1002/glia.22682

Summary: Postnatal and adult learning and memory require hippocampal neurogenesis. Cognitive dysfunction is frequently accompanied by neuroinflammatory pathogenesis, but the pathways by which the immune system affects neurogenesis are unclear. In this work the authors depleted microglia from primary hippocampal cultures by incubating the cells with 100 μg/ml Mac-1-SAP rat (Cat. #IT-33) for 24 hours. The hippocampal cells were then washed and cultured for further experiments. It was found that neural stem/progenitor cells had reduced survival and proliferation in cultures treated with Mac-1-SAP. These data sketch out the framework of an immune-neuronal pathway important in the regulation of hippocampal neurogenesis.

Related Products: Mac-1-SAP rat (Cat. #IT-33)

CD4+ T lymphocytes interact with microglia to modulate hippocampal neurogenesis.

Khan D, Owens E, Zaben M, Dunnett SB, Gray WP (2013) CD4+ T lymphocytes interact with microglia to modulate hippocampal neurogenesis. Neuroscience 2013 Abstracts 699.04. Society for Neuroscience, San Diego, CA.

Summary: Hippocampal neurogenesis occurs within the subgranular zone of the dentate gyrus and is important for learning and memory. Neurogenesis is impaired in patients with chronic temporal lobe epilepsy, an observation that may account for the learning and memory deficits that these patients commonly have. Emerging literature demonstrates that CD4+ T lymphocytes increase neurogenesis and enhance cognition; however, the exact mechanisms remain undetermined. Vasoactive Intestinal Peptide (VIP) receptors are expressed on T lymphocytes, microglia and hippocampal progenitor cells, hence this study was designed to investigate VIP’s role in mediating neuro-immune modulation. Hippocampal cultures (P7-10 Sprague Dawley rats) were generated and maintained for 3 days in vitro (DIV) and treated with 5% supernatant generated from C57/Bl6 mouse spleen using a CD4+ T lymphocyte isolation kit. BrdU and experimental conditions were added for the terminal 6 hours before fixation and then processed for BrdU and nestin. For phenotype analysis, experimental conditions were added at 3DIV and fixed at 6DIV to be processed for nestin and TuJ1. To deplete microglia, Mac-1-SAP was added at 2DIV for 24 hours before experimental conditions were added. 5% T lymphocytes supernatant increased proliferation of hippocampal nestin-expressing cells; an effect that is further enhanced under VIP treatment via VPAC1 receptor subtype. Examining potential cytokine mediators of this effect, PCR analysis showed 6-fold increase in IL-4 mRNA expression, and IL-4 antagonist abolished VIP proliferative effects. Using Mac-1-SAP to account for microglial involvement by depleting microglia, VIP proliferative effects were abolished. Our phenotyping studies also demonstrated an additional neurogenic effect under VIP treated supernatant compared to standard control conditions. Taken together, these results show VPAC1 receptor subtype expressed by CD4+ T lymphocytes mediates VIP proliferative effects on hippocampal cells via IL-4 cytokine release. Microglia mediates VIP proliferative effects. While we demonstrated before that VPAC2 mediates hippocampal progenitor cell survival, the findings of this study strongly implicate VPAC1 receptor as a neuro-immune mediator of hippocampal neurogenesis, and from a therapeutic perspective, shows that the effect can be pharmacologically manipulated.

Related Products: Mac-1-SAP rat (Cat. #IT-33)

ATS Poster of the Year Winner

Male and female mice use distinct spinal immune cells to mediate chronic pain.

Sorge RE, Martin LJ, Alexander J, Beggs S, Rosen S, Zhang J, Salter MW, Mogil JS (2013) Male and female mice use distinct spinal immune cells to mediate chronic pain. Neuroscience 2013 Abstracts 642.11. Society for Neuroscience, San Diego, CA.

Summary: There are clear sex differences in the sensitivity to painful stimuli and analgesics in humans and animals. Some data suggest that pain processing is mediated by separable pathways in male and female mice, for example we recently demonstrated that spinal cord toll-like receptor 4 is used to mediate chronic pain in male, but not female mice. Here, we sought to investigate the sex-dependent pathways involved in spinal mediation of pain in male and female mice. First, we found that allodynia induced by complete Freund’s adjuvant (CFA) or spared nerve injury (SNI) was reversible via intrathecal glial inhibitors (minocycline, 0-300 μg; fluorocitrate, 0-1.5 nmol; propentofylline, 0-75 μg), or glial cell depletion using Mac1-saporin, only in male mice and never in intact female mice. This suggests that female mice utilize a microglia-independent spinal pathway to mediate chronic pain. To investigate whether T cells might mediate chronic pain in female mice, we used two strains of T cell-deficient animals; Rag1 (Rag1tm1Mom) and nude CD1 (Crl: CD1-Foxn1nu). In both strains, SNI- or CFA-induced allodynia was reversible in female mice by glial inhibitors, similar to male mice. This effect was prevented through adoptive transfer of wild type (C57BL/6) splenocytes to Rag1 female mice, suggesting T-cell involvement. T-cell infiltration into the CNS was reduced with an antibody to β1-integrin; this manipulation transiently reversed allodynia in female mice, but not male mice, further confirming that T cells mediate chronic pain in females. Finally, castration was found to reduce the anti-allodynic effect of glial inhibitors and enhanced the potential of anti-β1 integrin in male mice. In contrast, ovariectomy with testosterone replacement in female mice eliminated the effect of anti-β1 integrin and enhanced the effect of glial inhibitors. We have uncovered a robust, qualitative, and previously unknown sex difference in spinal mediation of chronic pain in mice. Attention to this critical sex difference in pain mediation may be vital to future pharmaceutical development and to interpretation of clinical pain treatments that focus on one system or the other in a mixed-sex population.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis.

Ferrini F, Trang T, Mattioli TA, Laffray S, Del’Guidice T, Lorenzo LE, Castonguay A, Doyon N, Zhang W, Godin AG, Mohr D, Beggs S, Vandal K, Beaulieu JM, Cahill CM, Salter MW, De Koninck Y (2013) Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis. Nat Neurosci 16(2):183-192. doi: 10.1038/nn.3295

Summary: Although morphine is the drug of choice in dealing with chronic pain, it paradoxically can produce a hyperalgesic state. The authors examined the issue from several different angles. One method was to eliminate spinal microglia of rats through the intrathecal application of 16-32 μg of Mac-1-SAP (Cat. #IT-33). 20 μg of saporin (Cat. #PR-01) was used as a control. It was found that P2X4 receptors expressed by microglia were necessary for the development of morphine hyperalgesia, but not morphine tolerance.

Related Products: Mac-1-SAP rat (Cat. #IT-33), Saporin (Cat. #PR-01)

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Embryonic stem cell-derived neural stem cells fuse with microglia and mature neurons.

Cusulin C, Monni E, Ahlenius H, Wood J, Brune J, Lindvall O, Kokaia Z (2012) Embryonic stem cell-derived neural stem cells fuse with microglia and mature neurons. Stem Cells 30:2657-2671. doi: 10.1002/stem.1227

Summary: The fusogenic role of microglia could be even more important after NSC transplantation into brains affected by neurodegenerative diseases associated with microglia activation.

Usage: Primary Cells and NS Cell Coculture. Seven to twelve days after plating primary cells, NS cells were plated on top (10,000 cells per cm2)  for 1–3 days. Rat primary cells were treated with 10 nM Mac-1-SAP or Mouse IgG-SAP during the 5 days prior to the coculture, and analyzed 3 days thereafter.

Related Products: Mac-1-SAP rat (Cat. #IT-33), Mouse IgG-SAP (Cat. #IT-18)

Selective depletion of Mac-1-expressing microglia in rat subventricular zone does not alter neurogenic response early after stroke.

Heldmann U, Mine Y, Kokaia Z, Ekdahl CT, Lindvall O (2011) Selective depletion of Mac-1-expressing microglia in rat subventricular zone does not alter neurogenic response early after stroke. Exp Neurol 229(2):391-398. doi: 10.1016/j.expneurol.2011.03.005

Summary: One result of ischemic stroke is migration of newly formed neuroblasts into the injured area from the subventricular zone (SVZ). The authors investigated the role of microglia, which also accumulate in the SVZ after stroke, in this process. Rats received 5-µg or 10-µg intracerebroventricular injections of Mac-1-SAP (Cat. #IT-33) with varying schedules as to injection and sacrifice. The data indicate that the presence of microglia after stroke does not affect the number or migration of neuroblasts from the SVZ.

Related Products: Mac-1-SAP rat (Cat. #IT-33)

The role of microglia and neuropeptides in regulating hippocampal neurogenesis.

Sivasathiaseelan H, Nunan R, Zaben M, Shtaya A, Gray WP (2009) The role of microglia and neuropeptides in regulating hippocampal neurogenesis. Neuroscience 2009 Abstracts 31.26/B52. Society for Neuroscience, Chicago, IL.

Summary: Adult mammalian neurogenesis is evident in the hippocampal dentate gyrus where it plays a role in learning and memory and is implicated in the pathophysiology of several brain disorders. Microglia, the innate immune cells of the brain, have recently emerged as an important component of the neurogenic niche, however their role in the regulation of neurogenesis under physiological and pathophysiological conditions is a matter of debate. The aim of this study is to investigate the effect of microglia on hippocampal neurogenesis and to look at how vasoactive intestinal peptide (VIP), a potent immunomodulatory neuropeptide found in dentate gyrus interneurons, modulates the effects microglia have on neurogenesis. In this study, we have investigated the effect of microglial depletion (using MAC-SAP), microglial co-culture and addition of microglia-conditioned-medium on primary hippocampal cell cultures derived from post-natal rats. We have also looked at how pre-treatment of microglia with VIP alters their effect on hippocampal cultures. Bromodeoxyuridine was used as a marker of cell proliferation. Quantification of cell death was achieved using the nuclear stain 4',6-diamidino-2-phenylindole and Propidium Iodide. Immunohistochemistry was used to phenotype cells for nestin, GFAP and Tuj1. We have shown that microglial depletion results in a reduction in the numbers of nestin, GFAP and Tuj1 expressing cells. This reduction has been shown to be attributable to a decrease in cell survival and proliferation. Conversely, co-culture of microglia with hippocampal neurons or addition of their conditioned medium results in increased cell survival and proliferation. Pre-treatment of microglia with VIP was shown to increase both their proliferative and trophic effect on hippocampal cultures. In conclusion, this study demonstrates that microglia induce proliferative and trophic effects on neural stem cells and immature neurons through the release of soluble factors. Furthermore, we provide evidence that VIP regulates the release of these soluble factors, thus identifying a novel neuro-immuno-neurogenic link.

Related Products: Mac-1-SAP rat (Cat. #IT-33)

Immunotoxic depletion of microglia in mouse hippocampal slice cultures enhances ischemia-like neurodegeneration.

Montero M, Gonzalez B, Zimmer J (2009) Immunotoxic depletion of microglia in mouse hippocampal slice cultures enhances ischemia-like neurodegeneration. Brain Res 1291:140-152. doi: 10.1016/j.brainres.2009.06.097

Summary: Data has shown microglia to be both neuroprotective and neurodegenerative in cerebral ischemia. This study presents a method for removing microglia from hippocampal slice cultures. Hippocampal slices from mouse were incubated with 13 nM Mac-1-SAP (Cat. #IT-06) for 3 to 7 days. The slices were then exposed to oxygen-glucose deprivation. Those cultures lacking microglia displayed significantly higher degeneration of CA1 pyramidal cells, indicating a neuroprotective role for microglia in this model.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Read the featured article in Targeting Trends.

Neuroprotective effects of the anti-inflammatory compound triflusal on ischemia-like neurodegeneration in mouse hippocampal slice cultures occur independent of microglia.

Montero Dominguez M, Gonzalez B, Zimmer J (2009) Neuroprotective effects of the anti-inflammatory compound triflusal on ischemia-like neurodegeneration in mouse hippocampal slice cultures occur independent of microglia. Exp Neurol 218:11-23. doi: 10.1016/j.expneurol.2009.03.023

Summary: In this work the authors looked to clarify the role of microglia in an experimental stroke model. Hippocampal slices were subject to oxygen-glucose deprivation to establish the stroke model. Slices were exposed to 1.3 nM Mac-1-SAP (Cat. #IT-06) for 7 days prior to the experiments. This treatment depleted virtually all of the microglia. The lesioned slices were more susceptible to neurodegeneration, but the anti-inflammatory drug triflusal was still able to fulfill its neuroprotective role in treated slices.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Read the featured article in Targeting Trends.

ERK1/2 regulates microglia-neuron signaling and pain by PGE2 following SCI

Hains BC, Zhao P, Waxman S (2007) ERK1/2 regulates microglia-neuron signaling and pain by PGE2 following SCI. Neuroscience 2007 Abstracts 287.16/LL14. Society for Neuroscience, San Diego, CA.

Summary: We recently showed that microglia become activated after experimental SCI and dynamically maintain hyperresponsiveness of spinal cord nociceptive neurons and pain-related behaviors. Mechanisms of signaling between microglia and neurons that help to maintain abnormal pain processing are unknown. In this study, adult male Sprague Dawley rats underwent T9 spinal cord contusion injury. Four weeks after injury when lumbar dorsal horn multireceptive neurons became hyperresponsive and when behavioral nociceptive thresholds to mechanical and thermal stimuli were decreased, we tested the hypothesis that prostaglandin E2 (PGE2) contributes to signaling between microglia and neurons. Immunohistochemical data showed specific localization of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), an upstream regulator of PGE2 release, to microglial cells and a neuronal localization of the PGE2 receptor E-prostanoid 2 (EP2). Enzyme immunoassay analysis showed that PGE2 release was dependent on microglial activation and ERK1/2 phosphorylation. Pharmacological antagonism of PGE2 release was achieved with the mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor PD98059 and the microglial inhibitor minocycline. Cyclooxygenase-2 expression in microglia was similarly reduced by MEK1/2 inhibition. PD98059 and EP2 receptor blockade with AH6809 resulted in a decrease in hyperresponsiveness of dorsal horn neurons and partial restoration of behavioral nociceptive thresholds. Selective targeting of dorsal horn microglia with the Mac-1-SAP immunotoxin resulted in reduced microglia staining, reduction in PGE2 levels, and reversed pain-related behaviors. On the basis of these observations, we propose a PGE2-dependent, ERK1/2-regulated microglia-neuron signaling pathway that mediates the microglial component of pain maintenance after injury to the spinal cord.

Related Products: Mac-1-SAP rat (Cat. #IT-33)

A limited role for microglia in antibody mediated plaque clearance in APP mice.

Garcia-Alloza M, Ferrara BJ, Dodwell SA, Hickey GA, Hyman BT, Bacskai BJ (2007) A limited role for microglia in antibody mediated plaque clearance in APP mice. Neurobiol Dis 28(3):286-292. doi: 10.1016/j.nbd.2007.07.019

Summary: Microglia are thought to play a key role in the clearance of amyloid-b (Ab) in Alzheimer’s disease. To examine this role the authors applied 30 µl of 0.5 mg/ml Mac-1-SAP (Cat. #IT-06) to the brain surface of mice for 20 minutes. The number of microglia and plaques was determined by counting of immunohistochemical samples. Results indicate that microglia play a minor role in clearing Ab plaques, although the interaction of microglia-mediated inflammation and anti-Ab antibodies appears to be vital in this process.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Reactive oxygen species generation by the ethylene-bis-dithiocarbamate (EBDC) fungicide mancozeb and its contribution to neuronal toxicity in mesencephalic cells.

Domico LM, Cooper KR, Bernard LP, Zeevalk GD (2007) Reactive oxygen species generation by the ethylene-bis-dithiocarbamate (EBDC) fungicide mancozeb and its contribution to neuronal toxicity in mesencephalic cells. Neurotoxicology 28:1079-1091. doi: 10.1016/j.neuro.2007.04.008

Summary: This work explores the mechanisms of neuronal damage associated with the ethylene-bis-dithiocarbamate fungicide mancozeb (MZ). In order to obtain a purified rat mesencephalic culture, the authors treated neuronal cultures with Mac-1-SAP (Cat. #IT-33) at a final concentration of 2 µg/ml. The microglia-free cultures did not display attenuated reactive oxygen species (ROS) production when treated with MZ. The data suggest that microglia are not required for ROS production in the presence of MZ.

Related Products: Mac-1-SAP rat (Cat. #IT-33), Antibody to Mac-1 (Cat. #AB-N06)

Extracellular signal-regulated kinase-regulated microglia-neuron signaling by prostaglandin E2 contributes to pain after spinal cord injury.

Zhao P, Waxman SG, Hains BC (2007) Extracellular signal-regulated kinase-regulated microglia-neuron signaling by prostaglandin E2 contributes to pain after spinal cord injury. J Neurosci 27:2357-2368. doi: 10.1523/JNEUROSCI.0138-07.2007

Summary: Spinal cord injury frequently leads to the development of long-term chronic pain. Recent data has shown that activated microglia are involved in the maintenance of this pain state. Following a spinal cord contusion injury rats were treated with a 36-µg injection of Mac-1-SAP (Cat. #IT-06) into the lumbar enlargement. Treated animals were found to have reduced microglial staining, reduction in prostaglandin E2 levels, and fewer pain-related behaviors.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), , Antibody to Mac-1 (Cat. #AB-N06)

Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis.

Kanai T, Uraushihara K, Totsuka T, Nemoto Y, Fujii R, Kawamura T, Makita S, Sawada D, Yagita H, Okumura K, Watanabe M (2006) Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis. J Gastroenterol Hepatol 21(7):1136-1142. doi: 10.1111/j.1440-1746.2006.04391.x

Summary: Crohn’s disease is characterized by massive infiltration of macrophages and CD4(+) T-cells in the colon and small intestine. Using SCID mice, the authors evaluated the effects of Mac-1-SAP (Cat. #IT-06) on the development of chronic colitis. After transfer of T cells to the mice, 12.5 µg of Mac-1-SAP was injected into the intraperitoneal space. The reduction in CD4(+) T-cell infiltration of the colon, and suppression of IFNg and TNFa production indicate that macrophages play a significant role in the pathogenesis of Crohn’s disease.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Early microglial activation following neonatal excitotoxic brain damage in mice: a potential target for neuroprotection.

Dommergues MA, Plaisant F, Verney C, Gressens P (2003) Early microglial activation following neonatal excitotoxic brain damage in mice: a potential target for neuroprotection. Neuroscience 121(3):619-628. doi: 10.1016/s0306-4522(03)00558-x

Summary: Brain lesions that mimic damage from cerebral palsy in mice are characterized by microglial activation within 24 hours of insult. Using intraperitoneal injections of Mac-1-SAP (90 µg/kg, Cat. #IT-06), a reduction in the density of resident microglial and blood-derived monocytes was obtained.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Macrophage-derived IL-18 targeting for the treatment of Crohn’s disease.

Kanai T, Uraushihara K, Okazawa A, Hibi T, Watanabe M (2003) Macrophage-derived IL-18 targeting for the treatment of Crohn's disease. Curr Drug Targets Inflamm Allergy 2(2):131-136. doi: 10.2174/1568010033484250

Summary: A single intravenous injection of Mac-1-SAP (Cat. #IT-06) significantly reduced the amount of intestinal inflammation in a 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis model.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Reduction of microglia cell populations before induction of excitotoxicity reduces neurodegeneration.

Sheehan JJ, Tsirka SE (2002) Reduction of microglia cell populations before induction of excitotoxicity reduces neurodegeneration. Neuroscience 2002 Abstracts 606.9. Society for Neuroscience, Orlando, FL.

Summary: Excitotoxicity is thought to be a component of many neurodegenerative diseases including Alzheimer's and stroke. In excitotoxicity, as well as other injury models, microglia have been found to have both neuroprotective and neurodegenerative roles. To lend further insight into this controversy we utilized an immunotoxin selective for monocyte derived cell populations including microglia. The immunotoxin will selectively kill microglia and is not toxic to neurons or other glia populations in culture. In addition, infusion of the immunotoxin into the hippocampus of C57/Bl mice results in a selective reduction in endogenous microglial cell populations in this region. Furthermore, this reduction occurs without any perturbation of other cell types or the extracellular matrix. If depletion of microglia in this manner precedes excitotoxic injury, then hippocampal neurodegeneration is significantly reduced. These results agree with other work in our lab, which suggests that microglial cells exhibit neurotoxic properties in excitotoxicity.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Macrophage-derived IL-18-mediated intestinal inflammation in the murine model of Crohn’s disease.

Kanai T, Watanabe M, Okazawa A, Sato T, Yamazaki M, Okamoto S, Ishii H, Totsuka T, Iiyama R, Okamoto R, Ikeda M, Kurimoto M, Takeda K, Akira S, Hibi T (2001) Macrophage-derived IL-18-mediated intestinal inflammation in the murine model of Crohn’s disease. Gastroenterol 121:875-888. doi: 10.1053/gast.2001.28021

Summary: Crohn’s disease is an inflammatory bowel disease that is associated with several changes in the immune system, including an increased number of infiltrating macrophages. These macrophages release a variety of cytokines that are responsible for inflammation. The authors investigated the role of these macrophages in a mouse model by eliminating them with Mac-1-SAP (20 µg parenterally in tail vein; Cat. #IT-06). Seven days after treatment, mice showed no evidence of intestinal inflammation. These data demonstrate the role of macrophages in the development of inflammatory bowel conditions.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Mac-1-SAP rat (Cat. #IT-33)

Anatomical evidence for glial activation after intrathecal lumbosacral HIV-1 glycoprotein; gp120-induced allodynia.

Holguin A, Armstrong CB, Twining CM, Milligan ED, Hansen MK, McGorry M, O’Connor KA, Quan N, Martin D, Lappi DA, Maier SF, Watkins LR (2000) Anatomical evidence for glial activation after intrathecal lumbosacral HIV-1 glycoprotein; gp120-induced allodynia. Neuroscience 2000 Abstracts 733.4. Society for Neuroscience, New Orleans, LA.

Summary: Intrathecal (IT) HIV-1 glycoprotein, gp120: (a) produces thermal hyperalgesia & low threshold mechanical allodynia, and (b) increases interleukin-1β (IL1β) protein levels in lumbosacral (LS) spinal cord tissue & surrounding cerebrospinal fluid (CSF). Activated astrocytes & microglia (glia) release IL1β in response to gp120, and IT IL1 receptor antagonist or glial metabolic inhibitors prevent IT gp120-induced allodynia and thermal hyperalgesia. We determined whether IT gp120 produces glial activation and increased expression of glial IL1β as well as allodynia. LS spinal cord was collected 1.5 & 3 hrs after IT gp120 injection & verification of allodynia for immunocytochemistry (ICC) & in situ analysis of IL1β protein & mRNA. ICC for glial activation markers was performed 4,8 & 18 hrs after IT gp120 in LS & cervical spinal cords, as upregulation of these markers is delayed relative to behavioral changes. IT gp120 produced allodynia & increased IL1β protein ICC expression in LS spinal white (astrocytes) & gray matter (cells not identifiable) at 1.5 but not 3 hrs after injection. Increases in in situ IL1β mRNA were not detected. RT-PCR analysis of IL1β mRNA is underway. Glial activation (ICC) was observed in LS tissue 8 & 18 hrs after IT gp120. We are examining IT gp120 allodynia & hyperalgesia after an IT microglia-specific toxin (Saporin-linked Mac-1 antibody) injection that disrupts glial function. ICC procedures will verify Mac-1 Saporin microglial toxicity.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Elimination of microglia suggests their involvement in neuronal plasticity.

Siddiq MM, Tsirka SE (2000) Elimination of microglia suggests their involvement in neuronal plasticity. Neuroscience 2000 Abstracts 507.2. Society for Neuroscience, New Orleans, LA.

Summary: Reorganization of mossy fibers occurs in the mammalian hippocampus during consolidation of learning and memory. Induced low level seizures with kainic acid (KA) result in the development of new synapses and the reorganization of existing ones along the mossy fiber pathway. The serine protease tissue plasminogen activator (tPA) is expressed along the mossy fiber pathway and has been implicated in neurite remodeling after stimulation of neuronal activity. Both neurons and microglia secrete tPA. Microglial cells are thought to function only in pathological situations in the CNS, as they exhibit neurotoxic properties. However, a protective role has been observed in the regenerating optic nerve, where intervening activated microglia were involved in tissue remodeling. To investigate whether there is a role for microglia in mossy fiber remodeling, microglia were eliminated in C57/BL6 mice by immunolesioning. The reorganization of mossy fibers was evaluated. Kainate-injected wild-type mice had pronounced mossy fiber reorganization in the dentate gyrus of the hippocampal formation as detected by Timm staining, while the immunolesioned mice had significantly less and shorter mossy fibers. It is therefore suggested that activated microglia may play a role in active remodeling of mossy fibers in the hippocampus after KA-induced seizures.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)