ComplmenReeptor magraopk40iomirS8c Buhl AM.Pleiman CM.Rickert RC and Cambier JC (1997 contribution of each receptor to this binding remains dc2+mobisationaaEpeinandM2c unclea 161897-19 CrassT,Raffetseder U.Martin Ur(6)Express ion and cloningof Function erentiated cihA5pan-bd nd lung M and Mul Esterl w (1998 conglutinin.via clusters of charged amino acids in the nito 163534-35425 collagenous tails of the ligands.Its affinity for Cla ir isotonic bufter relatively low,lying in the mic om N160-283)of 10071 evid nce that th thought to display similar specificity.at least in regard to heC-termin e102381239 Clq.MBL and SPA.gCIqR,on the other hand,reacts with C1q. pha ically in human che and tr ed by Clqinclude the 16M1929-193 phils,ROM production (neutrophils, sinophils and en CH.Antonsen S.Hnd( Th monocvtes). promotion of FcR- and CRI-mediated CDI1b/CDI8)in the of the immur nd fibroblast adhes w27:29142919 yes in sed IL-1 8(199% sites in production and modulation of immunoglobulin produ .Roper D.ry tion by B cell restilexistsomeconfisipnastocChR Arg206 high-aflinity sites of C5a and ROM production.ibrobast adhesion and platelet art GR.Lynch NJ.Day AJ.Schwaeble W]and Sim RB(17)The g site receptor (cell surface 73 been clearly emonstrated Th BP. the the above-mo with each other in man RCand Ross GD(196 otor type 3 (CDIIb thought to regulate Further Reading Bro vn EJ (1992)Comple .adhesion and phagocytosis Signalling CR2/TAPA-I The datb collagenous tail of Clq is inhibitable by PTX,wortmannin -segment receptor.An of Im PY2940 g involvemer ofaGprotein 30 Hey ors in the kina B(1994)The rol e in gproce shown to induce ch es in and Ca PP. Aus RG Lan influx in mouse fibroblasts. chkine MD and Fearon DT(1990)Deficie encies of human C3 References (CR1.CD35)and type 2(CR2.CD21). Petty HR and Todd RF 3rd (1 Biological Chemisir 27:2023120234. Leukocvte Biology 5:492494. ENCYCLOPEDIA OF LIFE SCIENCES/2001NaThere are approximately 4´105 receptors for C1q on monocytes and neutrophils, although the individual contribution of each receptor to this binding remains unclear. Function cC1qR binds C1q, mannan-binding lectin (MBL), lung surfactant protein A (SPA), collectin CL43 and bovine conglutinin, via clusters of charged amino acids in the collagenous tails of the ligands. Its affinity for C1q in isotonic buffer is relatively low, lying in the micromolar range. The binding occurs through a site in the S region (N160–283) of the receptor (Stuart et al., 1997). C1qRp is thought to display similar specificity, at least in regard to C1q, MBL and SPA. gC1qR, on the other hand, reacts specifically with C1q. The activities triggered by C1q include the induction of chemotaxis and chemokinesis in mast cells and neutro￾phils, ROM production (neutrophils, eosinophils and monocytes), promotion of FcR- and CR1-mediated phagocytosis (monocytes), increased expression of E￾selectin, VCAM-1 and ICAM-1 by endothelial cells, platelet aggregation and fibroblast adhesion, as well as inducing an antiproliferative response, depressed IL-1 production and modulation of immunoglobulin produc￾tion by B cells. There still exists some confusion as to which receptors are involved in these processes, although cC1qR and gC1qR have been implicated in neutrophil chemotaxis and ROM production, fibroblast adhesion and platelet aggregation, while the involvement of C1qRp in phagocy￾tosis has been clearly demonstrated. However, it is likely that the various receptors cooperate with each other in triggering the above-mentioned activities. In addition to triggering cellular activities cC1qR is also thought to regulate classical pathway activation of complement by preventing formation of the active C1 complex (C1q-C1r2-C1s2). Signalling The data available on signal transduction by the C1qR are extremely scant. Neutrophil chemotaxis mediated by the collagenous tail of C1q is inhibitable by PTX, wortmannin and LY294002, indicating involvement of a G protein and PI3 kinase in the signalling processes initiated by cC1qR and/or C1qRp. Stimulation via cC1qR has also been shown to induce changes in K+ conductance and Ca2+ influx in mouse fibroblasts. References Ames RS, Li Y, Sarau HM et al. (1996) Molecular cloning and characterisation of the human anaphylatoxin C3a receptor. Journal of Biological Chemistry 271: 20231–20234. Buhl AM, Pleiman CM, Rickert RC and Cambier JC (1997) Quantitative regulation of B cell signalling by CD19: selective requirement for PI3-kinase activation, inositol-1,4,5-triphosphate production and Ca2+ mobilisation. Journal of Experimental Medicine 186: 1897–1910. Crass T, Raffetseder U, Martin U et al. (1996) Expression and cloning of the human C3a anaphylatoxin receptor (C3aR) from differentiated U937 cells. European Journal of Immunology 26: 1944–1950. Dedio J, Jahnen-Dechent W, Bachmann M and Muller-Esterl W (1998) The multiligand-binding protein gC1qR, putative C1q receptor, is a mitochondrial protein. Journal of Immunology 160: 3534–3542. Dempsey PW, Allison MED, Srinivas A, Goodnow CC and Fearon DT (1996) C3d of complement as a molecular adjuvant: Bridging innate and acquired immunity. Science 271: 348–350. Naik N, Giannini E, Brouchon L and Boulay F (1997) Internalisation and recycling of the C5a anaphylatoxin receptor: evidence that the agonist-mediated internalisation is modulated by phosphorylation of the C-terminal domain. Journal of Cell Science 110: 2381–2390. Nepomuceno RR and Tenner AJ (1998) C1qRP, the C1q receptor that enhances phagocytosis, is detected specifically in human cells of myeloid lineage, endothelial cells and platelets. Journal of Immunology 160: 1929–1935. Nielsen CH, Antonsen S, Matthiesen SH and Leslie RGQ (1997) The roles of complement receptors type 1 (CR1, CD35) and type 3 (CR3, CD11b/CD18) in the regulation of the immune complex-elicited respiratory burst of polymorphonuclear leukocytes in whole blood. European Journal of Immunology 27: 2914–2919. Pettit EJ and Hallett MB (1998) Two distinct storage and release sites in human neutrophils. Journal of Leukocyte Biology 63: 225–232. Raffetseder U, Roper D,Mery L et al (1996) Site-directed mutagenesis of conserved charged residues in the helical region of the human C5a receptor. Arg206 determines high-affinity binding sites of C5a receptor. European Journal of Biochemistry 235: 82–90. Stuart GR, Lynch NJ, Day AJ, Schwaeble WJ and Sim RB (1997) The C1q and collectin binding site within C1q receptor (cell surface calreticulin). Immunopharmacology 38: 73–80. Thornton BP, Vetvicka V, Pitman M, Goldman RCand Ross GD (1996) Analysis of the sugar specificity and molecular location of the b￾glucan-binding lectin site of complement receptor type 3 (CD11b/ CD18). Journal of Immunology 156: 1235–1246. Further Reading Brown EJ (1992) Complement receptors, adhesion and phagocytosis. Infectious Agents and Disease 1: 63–70. Fearon DT and Carter RH (1995) The CD19/CR2/TAPA-1 complex of B lymphocytes: linking natural to acquired immunity. Annual Review of Immunology 13: 127–149. Gerard Cand Gerard NP (1994) C5A anaphylotoxin and its seven transmembrane-segment receptor. Annual Review of Immunology 12: 775–808. Heymann B (1994) The role of complement receptors in the regulation of the immune response. In: Erdei A (ed.) New Aspects of Complement Structure and Function, pp. 59–72. Austin: RG Landes. Hourcade D, Holers VM and Aktinson JP (1989) The regulators of complement activation (RCA) gene cluster. Advances in Immunology 45: 381–416. Kazatchkine MD and Fearon DT (1990) Deficiencies of human C3 complement receptors type 1 (CR1, CD35) and type 2 (CR2, CD21). Immunodeficiency Review 2: 17–41. Petty HR and Todd RF 3rd (1993) Receptor–receptor interactions of complement receptor type 3 in neutrophil membranes. Journal of Leukocyte Biology 54: 492–494. Complement Receptors 8 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net