Characterization of genetic defects in macrophage tumoricidal capacity: identification of murine strains with abnormalities in secretion of cytolytic factors and ability to bind neoplastic targets.

Peritoneal macrophages from BCG-infected C3H/HeJ or A/J mice, in contrast to BCG-activated macrophages from C3H/HeN mice, were ineffective at lysing adherent 1023 sarcoma targets, nonadherent P815 mastocytoma targets, or nonadherent EL-4 lymphoma targets. The ability of macrophages from BCG-infected C3H/HeJ mice to secret cytolytic factor (CF) into the supernatant medium was markedly impaired. This secretory deficit, however, did not extend to plasminogen activator, secretion of which was augmented. In contrast, the ability of BCG macrophages from A/J mice to secrete CF was comparable to or even slightly higher than that of macrophages from C3H/HeN mice. The ability of BCG-elicited macrophages from A/J mice to bind either of 2 neoplastic targets (the P815 mastocytoma and the EL-4 lymphoma), however, was greatly reduced. The ability of BCG-elicited macrophages from C3H/HeJ mice to bind these targets was comparable to that of macrophages from C3H/HeN mice. The data suggest that the phenotypically-similar deficits in tumoricidal capacity of BCG-elicited macrophages from C3H/HeJ and A/J mice are mediated by mechanistically different defects in macrophage-tumor cell interactions.