Macrophage Tumoricidal Activity Induced By Human C-Reactive Protein1

Purified C-reactive protein (CRP), the prototypical acute phase reactant of humans, activated inflammatory mouse macrophages to a tumoricidal state. The activation by CRP was not due to small amounts of contaminating lipopolysaccharide. CRP at 10 fig/ml induced significant tumoricidal capacity in resident macrophages; the mouse macrophage cell lines PUS 1.8, RAW 264.7, and J774; as well as elicited macrophages from two lipopolysaccharide nonresponder strains, C3H/HeJ and C57BL/10SC. Macrophages obtained from bone marrow-derived monocytes grown in vitro and exÃodate macrophages depleted of T-cells were also readily activated by Mg/ml amounts of CRP. Removal of CRP from culture medium using anti-CRP antibodies or phosphorylcholine-agarose beads abrogated the induction of tumoricidal activity. CRP acted inde pendently of both lymphokines and lipopolysaccharide. Therefore, CRP may serve as a physiologically relevant macrophage activator, contrib uting to the heightened nonspecific host resistance associated with the early stages of a systemic inflammatory response.