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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)
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)
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)
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)
Featured Article: Depletion of microglia by Mac-1-SAP in mouse hippocampal slice cultures enhances ischemia-like neurodegeneration
Montero M, Gonzalez B, Zimmer J (2009) Featured Article: Depletion of microglia by Mac-1-SAP in mouse hippocampal slice cultures enhances ischemia-like neurodegeneration. Targeting Trends 10(3)
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)
Read the featured article in Targeting Trends.
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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)
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)
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 PMID: 17329433
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)