- Home
- Knowledge Base
- References
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)