Complement anaphylatoxin receptors on neurons: new tricks for old receptors?

Abstract

398 TINS Vol. 22, No. 9, 1999 of histamine and other vasoactive amines); increased vascular permeability; degranulation of phagocytic cells; generation of superoxide radicals; induction of pro-inflammatory cytokine synthesis; and acute-phase protein production2–4. Although C3a elicits a similar, but smaller, range of inflammatory responses4, it is likely that following the recent cloning of C3aR (Refs 5–7) additional inflammatory functions will be uncovered for C3a in the near future. The C3a and C5a receptors The functional responses mediated by C3a and C5a are a result of binding to C3aR and C5aR, respectively. These receptors are members of the rhodopsin family of G-protein-coupled receptors (Fig. 1)2–4,6,8,9. The human C3aR and C5aR share 37% nucleotide identity, with most of the homology occurring in the transmembrane regions (TM) and in the second intracellular loop. The C3aR is unique among the receptors of this family in that it has an unusually large extracellular domain between TM4 and TM5 (over 160 amino-acid residues)5,6. The C3aR and C5aR are encoded by single copy genes. The human C5aR is located on chromosome 19 in a region that contains the genes for several chemoattrac- tant receptors10,11, while the gene encoding the human C3aR is located on chromosome 12 (Ref. 12). The expression of the genes for C3aR and C5aR was, until recently, thought to be restricted largely to cells of the myeloid lineage, such as neutrophils, macrophages, eosinophils, basophils and mast cells3,4. However, in recent years, studies have demonstrated widespread localization of these receptors throughout many tissue and cell types outside the immune system3–6. The recent findings demonstrating that astrocytes, microglia and, surprisingly, neurons possess C3aR and C5aR (Refs 13–19) are of most interest for this article. The presence of C3aR and C5aR on microglia was expected owing to the monocytic origin of these cells20. Similarly, the pres- ence of these receptors on astrocyte

Key Biomarkers

Symptom Clusters