title: The contribution of gC1qR/p33 in infection and inflammation.
abstract: Human gC1qR/p33 is a multi-compartmental and multi-functional cellular protein expressed on a wide range of tissues and cell types including lymphocytes, endothelial cells, dendritic cells, and platelets. Although originally isolated as a receptor for C1q by virtue of its affinity (K(d)=15-50 nM), and specificity for the globular heads of this molecule, a large body of evidence has now been accumulated which shows that in addition to C1q, gC1qR can serve as a receptor for diverse proinflammatory ligands including proteins of the plasma kinin-forming system, most notably high molecular weight kininogen (HK; K(d)=9 nM). In addition, gC1qR has been reported to recognize and bind a number of functional antigens of viral and bacterial origin. It is its ability to interact with microbial antigens and its potential to serve as a cellular protein for bacterial attachment and/or entry that has been the focus of our laboratory in the past few years. On the surface of activated platelets, gC1qR has been shown to serve as a binding site for Staphylococcus aureus and this binding is mediated by protein A. Since the binding of S. aureus to platelets is postulated to play a major role in the pathogenesis of endocarditis, gC1qR may provide a suitable surface for the initial adhesion of the bacterium. Recent data also demonstrate that the exosporium of Bacillus cereus, a member of a genus of aerobic, Gram-positive, spore-forming rod-like bacilli, which includes the deadly Bacillus anthracis, contains a binding site for gC1qR. Therefore, by virtue of its ability to recognize plasma proteins such as C1q and HK, as well as bacterial and viral antigens, cell-surface gC1qR not only is able to generate proinflammatory byproducts from the complement and kinin/kallikrein systems, but also can be an efficient vehicle and platform for a plethora of pathogenic microorganisms.
authors.affiliation: Department of Pathology, Weill Medical College of Cornell University, New York Presbyterian Hospital, 525 East 68th Street, Room F715, NY 10021, USA. epeersch@med.cornell.edu
authors.forename: Ellinor I B
authors.initials: EI
authors.lastname: Peerschke
authors.forename: Berhane
authors.initials: B
authors.lastname: Ghebrehiwet
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001920:Bradykinin / Q000096:biosynthesis; D003165:Complement System Proteins / Q000378:metabolism; D006801:Humans; D007239:Infections / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011951:Receptors, Complement / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D008562:Membrane Glycoproteins; D011951:Receptors, Complement; C032402:complement 1q receptor; D003165:Complement System Proteins; D001920:Bradykinin