Post-translational control of complement (C5) production by resident and stimulated mouse macrophages.

Synthesis, secretion, and post-translational modification of C5 protein by mouse macrophages were examined in cultures of resident cells and exudates induced by thioglycollate or endotoxin. Synthesis of C5 was established by appearance of hemolytically active C5 in the media, by incorporation of radiolabeled amino acid into C5 protein, and by reversible inhibition of production in the presence of cycloheximide. Intracellular and extracellular radiolabeled C5 antigen and total protein synthesis were 2-fold greater in the thioglycollate-induced macrophage cultures than in the resident cell cultures. In contrast, the amount of hemolytically active C5 in resident cell culture medium was at least 4 to 5 times greater than that in stimulated cell culture medium; that is, specific functional activity of resident cell C5 was 8 to 10 times that of thioglycollate-induced cells. Co-cultures of stimulated and resident cells or mixing of conditioned media resulted in generation of up to three times the expected C5 activity. These data suggest that the amount of biologically active C5 secreted by inflammatory and resident macrophages is in large part under post-translational control, not a function solely of a change in synthesis rate.