| C-reactive protein (CRP) is an acute phase reactant which is found bound to cells at sites of inflammation. This project was undertaken to investigate closely the effect of binding of CRP to nucleated cells on selected host defense mechanisms. Using an in vitro system the effects of CRP binding to the nucleated HEp-2 cells on complement activation and lysis, lymphocyte natural killer (NK) and monocyte antibody dependent cell mediated cytotoxicity (ADCC) were examined.;CRP or an antigenically related molecule has been found on the surface of NK cells. To determine whether this CRP can function in the recognition of target cells for NK cytotoxicity, K562 cells (known NK targets) and HEp-2 cells were sensitized with protamine sulfate for CRP binding. Protamine or protamine and CRP treatment neither caused killing of HEp-2 cells nor enhanced killing of K562 cells in a standard NK cytotoxicity assay using human lymphocyte effectors.;CRP has been shown to bind to human peripheral blood monocytes. To determine whether this binding could lead to the recognition and subsequent killing of target cells in a reaction analogous to ADCC, HEp-2 cells were sensitized with protamine and CRP and added to human monocyte effectors in a cytotoxicity assay. Treatment of targets with protamine or protamine and CRP did not lead to killing by monocytes, whereas cells treated with rabbit antibody to HEp-2 cells were readily lysed by the effector cells.;These results suggest that CRP binding to nucleated cells does not lead to killing of these cells by the host defense mechanisms examined.;To investigate CRP mediated complement activation, HEp-2 cells were sensitized with protamine sulfate or phosphocholine (PC), two known CRP ligands, and under the conditions used bound 7 and 5 (mu)g CRP/5 x 10('5) cells respectively. These CRP treated cells activated the classical complement pathway in human serum, consuming > 80% of C1, C4 and C2, and about 30% of C3, but none of the later complement components. Control cells treated with anti-HEp-2 cell antiserum or antibody to PC consumed > 90% of C1, C4, C2, and 50-100% of the components C3 to C9 and were readily lysed by this activation. |
