Effects of endotoxins from Bacteroides intermedius and Escherichia coli on cytotoxic and lysosomal activity in peritoneal macrophages from endotoxin responder and low responder mouse strains.

Peritoneal macrophages from normal mice strains (C3H/Tif and C57BL/6J) and from the endotoxin (lipopolysaccharide, LPS) low responder strain (C3H/Hej were exposed to two structurally different endotoxins from Bacteroides intermedius and Escherichia coli in vitro. Intracellular activity of a lysosomal enzyme (acid phosphatase) and macrophage mediated cytotoxic activity against a tumor cell line (L929) were tested. Both endotoxins caused increased levels of acid phosphatase activity in normal mice macrophages. No change was obtained in the C3H/Hej macrophages exposed to E. coli LPS; however, the B. intermedius LPS was able to strongly elevate intracellular enzyme level in the C3H/Hej low responder macrophages. Cytotoxic activities were investigated in macrophage supernatants and in co-cultures of stimulated macrophages and target cells. Cytotoxic activity evaluated by measuring release of radioactivity from 14C-thymidine labelled tumor cells was increased with both endotoxins in normal mouse macrophages, but not in non-responder macrophages. When macrophage-mediated effects on tumor cells were tested by counting target cells left per culture, a reduction in target cell number was observed in endotoxin-treated low responder macrophage as well as in normal strain macrophage cultures more pronounced, however, in the normal strain. Cell contact between cytotoxic macrophages and target cells was verified by scanning electron microscopy. The results suggest that LPS effects on macrophages are dependent upon the functional parameters studied, and that the chemical composition of a particular LPS is important for its selective effects on macrophage functions.