Interactions of C-Reactive Protein with the First Component of Human Complement

Abstract

Abstract C-reactive protein (CRP), a trace constituent of serum which generally increases dramatically in concentration during reactions of inflammation and tissue destruction, has recently been shown to inhibit multiple functions of both T cells and platelets. Certain interactions of CRP in the presence of human serum have been shown to result in the efficient depletion of C components C1-5, and in the initiation of C-dependent adherence, phagocytosis, and cytolysis. In the present experiments, CRP was compared with antibody for the ability to react with the first component of human complement. Like IgG, CRP was found to bind purified C1̄ and this binding was markedly enhanced upon chemical aggregation or interaction of CRP with one of its binding specificities, the C-polysaccharide (CPS) of the pneumococcus. Both hemolytically active and native CI bound to CPS-coated erythrocytes (ECPS) sensitized with CRP (ECPS-CRP), and in both instances C1̄ could be recovered by transfer to EAC4; approximately equivalent amounts by weight of CRP and rabbit anti-CPS were required for these effects. The interaction between CRP and C1̄ occurred at the level of C1q, as shown by inhibition of binding and transfer of C1̄ by purified C1q, agglutination of ECPS-CRP by C1q and binding of 125I-C1q to ECPS-CRP. Thus, these results provide further evidence for the similarity of CRP to antibody in the nature of its interaction with the first component of human complement at the level of C1q, and support the concept that CRP may have an important role in the initiation and modulation of reactions of inflammation and host defense.