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Activation of Human Monocyte Tumoricidal Activity by C-reactive Protein¹

Department of Immunopathology [B. P. B., S. D. D.], The Cleveland Clinic Foundation, Cleveland, Ohio 44106, and Department of Pathology [K. J.], Central DuPage Hospital, Winfield, Illinois 60190

We examined the effect of purified human C-reactive protein (CRP) on induction of human peripheral blood monocyte (Mo)-mediated cytotoxicity (CTX) and oxidative metabolism. Exposure of Mo to acute phase serum levels of CRP in vitro resulted in dose-dependent expression of CTX against human tumor cell lines. Nonneoplastic human fibroblasts and glial cells were not affected by CRP-exposed Mo, and treatment of Mo monolayers with anti-Leu 11b (a natural killer marker) and complement did not abrogate or diminish CTX. Tumoricidal activity was observed after 20–44 h of Mo exposure to CRP, and after 48–72 h of coculture with radiolabeled target tumor cells. Mo exposed to CRP for 48 h also demonstrated elevated superoxide anion production when challenged with phorbol myristate acetate. Unlike CTX induced by lipopolysaccharide, CRP-induced CTX was completely inhibited by prein-cubation of CRP with phosphorylcholine, a CRP ligand, at a concentration of 5.5 molecules phosphorylcholine per molecule CRP. Further, when Mo medium (which contained 5% human AB serum) was preincubated with immobilized CRP, exposure of Mo to CRP in such medium did not result in CTX. In contrast, LPS-induced CTX was not affected. CRP-induced Mo CTX was observed, however, when Mo were exposed to CRP in medium preincubated with phosphorylcholine-treated immobilized CRP, suggesting that an active serum component which complexed with CRP was not removed. These findings indicate that one of the functions of the acute phase protein, CRP, may be to activate Mo and that the process may require a CRP-binding serum component.

¹ This investigation was supported in part by Grant 2R01-CA-33932 from the National Cancer Institute and by a grant from the American Cancer Society.

² To whom requests for reprints should be addressed, at Department of Immunopathology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44106.

Received 11/ 7/86. Revised 4/ 6/87. Accepted 5/ 2/87.

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