Binding of C-reactive protein to nucleated cells leads to complement activation without cytolysis.
C-reactive protein (CRP) is an acute-phase reactant that is found bound to cells at sites of inflammation. We have passively sensitized HEp-2 cells for CRP binding and examined the effect of this treatment on complement activation and cell lysis. When cells were treated with protamine sulfate and CRP and were incubated with normal human serum in a 4-hr 51Cr-release assay, no significant lysis was noted. In contrast, HEp-2 cells treated with antibody and normal human serum were lysed. The consumption of complement components in normal human serum after incubation with cells treated with protamine and CRP was measured by hemolytic assays. CRP-treated cells consumed over 80% of C1, C4, and C2 and about 40% of C3 present. No significant consumption of C5 through C9 components was observed. Cells treated with antibody and complement showed consumption of C1 through C9. Cells were also sensitized for CRP binding by using diazophenylphosphocholine. This treatment also led to CRP binding and activation of the early classical pathway (C1, C4, C2, and to a lesser extent C3). The components of the membrane attack complex (C5 through C9) were not activated. Both a mouse monoclonal IgM and a human IgG antibody to phosphocholine activated the entire classical pathway. These results indicate that CRP activation of the classical complement pathway is restricted to the early part of the pathway. In the absence of activation of the membrane attack complex, complement-mediated cell lysis cannot occur.
D000818:Animals; D000912:Antibodies, Neoplasm / Q000502:physiology; D001666:Binding Sites, Antibody; D002097:C-Reactive Protein / Q000378:metabolism*; D002277:Carcinoma / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D003167:Complement Activation / Q000187:drug effects; D003165:Complement System Proteins / Q000378:metabolism / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007822:Laryngeal Neoplasms / Q000276:immunology* / Q000378:metabolism; D010767:Phosphorylcholine / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011817:Rabbits
D000912:Antibodies, Neoplasm; D011479:Protamines; D010767:Phosphorylcholine; D003165:Complement System Proteins; D002097:C-Reactive Protein