Divergent expression of cytotoxic and microbicidal functions of rabbit alveolar and peritoneal macrophages: effects of non-specific activation and a natural microbicidal peptide, MCP-1.

Abstract

Alveolar macrophages from NZW rabbits were intrinsically toxic to 6 xenogeneic cell lines and to Candida albicans in vitro. Macrophage-mediated candidacidal activity, but not cytostasis (inhibition of [3H] thymidine incorporation by target cells) or cytotoxicity (reduction in target cell number), was enhanced by prior injection of rabbits with Freund's complete adjuvant (FCA). Compared with alveolar macrophages, peritoneal macrophages were less candidacidal (median C. albicans killed, 24% versus 16%, p less than 0.01). In contrast to alveolar macrophages, peritoneal macrophages were not consistently cytostatic or cytotoxic. Only candidacidal activity was enhanced in FCA-elicited peritoneal macrophages (median C. albicans killed 28% versus 16% for resident peritoneal macrophages, p less than 0.01). Microbicidal concentrations of a cationic peptide produced by rabbit alveolar macrophages (MCP-1, 25-100 micrograms/ml) did not inhibit growth of 4 murine cell lines in vitro. Macrophage-mediated cytostasis and cytotoxicity were not enhanced by culture with exogenous MCP-1. Macrophage-mediated cytostasis was also unchanged in cultures containing 10(-5) 2' deoxycytidine. We conclude that rabbit macrophage populations are restricted in their expression of cytostatic and cytotoxic functions, that microbicidal activation can occur independently of cytotoxic activation and that in this system mechanisms of macrophage-mediated cytotoxicity to xenogeneic target cells are independent of MCP-1 and thymidine.