Eur J Immunol 2002 Apr;32(4):1157-63
Reiman R, Gerard C, Campbell IL, Barnum SR.
Department of Microbiology, University of Alabama at Birmingham, Birmingham, USA.
Activation of the complement system generates the anaphylatoxic peptide C5a, which elicits a broad range of inflammatory activities.
The biological activities of C5a are mediated through its binding to the widely expressed C5a receptor (C5aR), a G-protein-coupled seven transmembrane domain receptor.
In experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, the C5aR is expressed on monocytes/macrophages, reactive astrocytes and T cells infiltrating the central nervous system (CNS).
To investigate the role of the C5aR in this T cell-driven autoimmunemodel, we induced EAE in C5aR-deficient mice (C5aR(-/-)) and wild-type mice using a myelin oligodendrocyte glycoprotein (MOG) peptide as the immunogen.
We found that C5aR(-/-) mice were fully susceptible to MOG-induced EAE with no difference in disease onset or severity in C5aR(-/-) mice compared to control mice.
Cellular infiltrates (macrophages and T cells) were similarin the spinal cords of both animal groups and splenic T cells from C5aR(-/-) mice and control mice responded identically to MOG in T cell proliferation assays.
Ribonuclease protection assays demonstrated no significant differences in pro-inflammatory gene expression between receptor-deficient and sufficient mice.
These results indicate that the C5aR is not an essential mediator in the induction and progression of EAE.