The contribution of gC1qR/p33 in infection and inflammation

Human gClqR/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 Clq by virtue of its affinity (K-d = 15-5nM), and specificity for the globular heads of this molecule, a large body of evidence has now been accumulated which shows that in addition to Clq, gClqR 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 = 9nM). In addition, gClqR 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, gClqR 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, gClqR 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 gClqR. Therefore, by virtue of its ability to recognize plasma proteins such as Clq and HK, as well as bacterial and viral antigens, cell-surface gClqR 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. (c) 2006 Elsevier GmbH. All rights reserved.