Disruption of the C5a receptor gene fails to protect against experimental allergic encephalomyelitis

Eur J Immunol. 2002 Apr;32(4):1157-63. doi: 10.1002/1521-4141(200204)32:4<1157::AID-IMMU1157>3.0.CO;2-M.

Abstract

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 autoimmune model, 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 similar in 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / physiology*
  • CD3 Complex / biosynthesis
  • CD3 Complex / genetics
  • Cells, Cultured / immunology
  • Chemokines / biosynthesis
  • Chemokines / genetics
  • Complement Activation
  • Complement C5a / physiology
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Disease Models, Animal
  • Disease Progression
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Lymphocyte Activation
  • Macrophage-1 Antigen / biosynthesis
  • Macrophage-1 Antigen / genetics
  • Macrophages / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microglia / pathology
  • RNA, Messenger / biosynthesis
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement / deficiency
  • Receptors, Complement / genetics
  • Receptors, Complement / physiology*
  • Spinal Cord / pathology
  • T-Lymphocyte Subsets / immunology

Substances

  • Antigens, CD
  • CD3 Complex
  • Chemokines
  • Cytokines
  • Macrophage-1 Antigen
  • RNA, Messenger
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement
  • Complement C5a