Resistance of macrophages from C3H/HeJ mice to the in vitro cytotoxic effects of endotoxin

Endotoxin (LPS) is toxic for normal mouse macrophages in vitro at concentrations (50 μg/ml) that are fully mitogenic and nontoxic to lymphocytes. Macrophages from LPS resistant C3H/HeJ mice are not killed by LPS in vitro whereas those from a closely related LPS responsive strain (C3H/HeN) are killed. Killing is the result of a direct interaction between LPS and the macrophage since this phenomenon is observed in lymphocyte depleted cultures and since the presence of additional LPS-sensitive spleen cells will not enhance the killing of either C3H/HeN or C3H/HeJ macrophages. Furthermore, C3H/HeJ macrophages remain resistant to LPS induced killing despite prior immunization with LPS in vivo or incubation with anti-LPS serum in vitro. LPS preparations vary in their cytotoxic effect on macrophages, and Escherichia coli K 235 LPS (phenol-water extracted), which discriminates well between LPS responsive and nonresponsive B cells, also discriminates well between LPS-sensitive and resistant macrophages. However, there is no apparent correlation between the mitogenic potential of LPS preparations and their cytotoxic effect on macrophages. These findings suggest that the C3H/HeJ mouse strain possesses a defect in LPS responsiveness which is intrinsic to its macrophages as well as its B lymphocytes.