Journal
JOURNAL OF IMMUNOLOGY
Volume 173, Issue 7, Pages 4708-4714Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.173.7.4708
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Funding
- NHLBI NIH HHS [HL074333] Funding Source: Medline
- NIAID NIH HHS [T32AI07041, AI020511] Funding Source: Medline
- NIMH NIH HHS [MH62231] Funding Source: Medline
- NINDS NIH HHS [NS46032, NS36979] Funding Source: Medline
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The C3aR is expressed throughout the CNS and is increased in expression on glial cells during CNS inflammation. However, the role that C3a and the C3aR play in chronic inflammation, such as in the demyelinating disease experimental autoimmune encephalomyelitis (EAE), remains unclear. We show in this study that deletion of the C3aR is protective in myelin oligodendrocyte glycoprotein-induced EAE in C57BL/6 mice. C3aR-deficient (C3aR(-/-)) mice had a significantly attenuated course of EAE compared with control mice during the chronic phase of the disease. Immunohistochemical analysis demonstrated modestly reduced macrophage and T cell infiltration in the spinal cords of C3aR-/- mice. To examine the role of C3a in EAE, we developed a transgenic mouse that expresses C3a exclusively in the CNS using the glial fibrillary acidic protein (GFAP) promoter. We observed that C3a/GFAP mice had exacerbated EAE during the chronic phase of the disease, with significant mortality compared with nontransgenic littermates. C3a/GFAP mice had massive meningeal and perivascular infiltration of macrophages and CD4(+) T cells. These studies indicate that C3a may contribute to the pathogenesis of demyelinating disease by directly or indirectly chemoattracting encephalitogenic cells to the CNS.
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