title: Human C1qRp is identical with CD93 and the mNI-11 antigen but does not bind C1q.
abstract: It has been suggested that the human C1qRp is a receptor for the complement component C1q; however, there is no direct evidence for an interaction between C1q and C1qRp. In this study, we demonstrate that C1q does not show enhanced binding to C1qRp-transfected cells compared with control cells. Furthermore, a soluble recombinant C1qRp-Fc chimera failed to interact with immobilized C1q. The proposed role of C1qRp in the phagocytic response in vivo is also unsupported in that we demonstrate that this molecule is not expressed by macrophages in a variety of human tissues and the predominant site of expression is on endothelial cells. Studies on the rodent homolog of C1qRp, known as AA4, have suggested that this molecule may function as an intercellular adhesion molecule. Here we show that C1qRp is the Ag recognized by several previously described mAbs, mNI-11 and two anti-CD93 Abs (clones X2 and VIMD2b). Interestingly, mNI-11 (Fab') has been shown to promote monocyte-monocyte and monocyte-endothelial cell adhesive interactions. We produced a recombinant C1qRp-Fc chimera containing the C-type lectin-like domain of C1qRp and found specific binding to vascular endothelial cells in sections of inflamed human tonsil, indicating the presence of a C1qRp ligand at this site. This interaction was Ca(2+) independent and was not blocked by our anti-C1qRp mAb BIIG-4, but was blocked by the proadhesive mAb mNI-11. Collectively, these data indicate that C1qRp is not a receptor for C1q, and they support the emerging role of C1qRp (here renamed CD93) in functions relevant to intercellular adhesion.
authors: Brain Inflammation and Immunity Group, Department of Medical Biochemistry, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, Wales, UK. gasque@cf.ac.uk
authors: Eamon P
authors: EP
authors: McGreal
authors: Nobunao
authors: N
authors: Ikewaki
authors: Hiroyasu
authors: H
authors: Akatsu
authors: B Paul
authors: BP
authors: Morgan
authors: Philippe
authors: P
authors: Gasque
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000918:Antibody Specificity; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism*; D016466:CHO Cells; D002352:Carrier Proteins; D002460:Cell Line; D015922:Complement C1q / Q000378:metabolism*; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors; D007106:Immune Sera / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D037181:Lectins, C-Type; D008024:Ligands; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins; D051379:Mice; D024101:Mitochondrial Proteins; D014066:Palatine Tonsil / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000276:immunology; D051381:Rats; D011951:Receptors, Complement / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000378:metabolism*; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C087299:C1QBP protein, human; C490193:C1qbp protein, mouse; C490195:C1qbp protein, rat; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D007106:Immune Sera; D007074:Immunoglobulin G; D037102:Lectins; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; D011993:Recombinant Fusion Proteins; D012795:Sialoglycoproteins; C032402:complement 1q receptor; D015922:Complement C1q