Interactions of Human C1̄ with C-Reactive Protein and Polyanion-Polycation Complexes

Abstract

Abstract C-reactive protein (CRP) is a potent activator of the classical C pathway when reacting with C-polysaccharide (CPS), choline phosphatides and certain polycations. Using a C1̄ binding assay we have shown that, like IgG, native CRP can bind purified human C1̄. This binding was increased approximately 10-fold when CRP was aggregated by heat or bis-diazotized benzidine treatment or when CRP was combined with its substrates including CPS and protamine sulfate. Human C1̄ was found to bind to and transfer from CPS-sensitized E pretreated with CRP (E-CPS-CRP) as well as with anti-CPS (rabbit) IgG, indicating that this interaction involved the C1̄ macromolecule, and suggesting participation of C1q; agglutination of E-CPS-CRP by purified C1q supported this conclusion. In agreement with earlier experiments performed in whole serum, interaction of polyanions (e.g., heparin) and polycations (e.g., protamine and poly-l-lysine) resulted in substantial C1̄ binding independent of the presence of immunoglobulins. This was quantitatively increased in the presence of CRP, and CRP markedly enhanced C consumption induced by interaction of these counterions in whole serum, suggesting that CRP may have an important role in C consumption by polyanion-polycation complexes.