Lipopolysaccharide (LPS)-induced cell death of C3H mouse peritoneal macrophages in the presence of cycloheximide: different susceptibilities of C3H/HeN and C3H/HeJ mice macrophages

Lipopolysaccharide (LPS) induced cytotoxicity toward mouse peritoneal macro phages from C3H/HeN mice but not C3H/HeJ mice in vitro in the presence of c ycloheximide (CHX). More than 1 ng/ml LPS induced a significant time-depend ent release of a cytoplasmic enzyme, lactate dehydrogenase (LDH), while eve n 1000 ng/ml LPS failed to induce it in LPS-non-responsive C3H/HeJ mouse ma crophages. Although similar LPS-induced cytotoxicity was observed in a muri ne macrophage-like cell line, J774.1,but not in an LPS-resistant mutant of J774.1, the LPS 1916 cell line, these results suggest that the induction of this cytotoxicity is linked to the LPS-sensitivity of mouse macrophages. A recombinant TNF-alpha (rTNF-alpha) at 100 ng/ml augmented LDH release from both C3H/HeN and C3H/HeJ macrophages treated with LPS and CHX, while rTNF- alpha alone or in combination with LPS or CHX failed to induce LDH release. These results suggest that this cytotoxicity might be partially regulated by high concentrations of exogenous TNF-alpha in both C3HMeN and C3H/HeJ ma crophages, implying a possibility of paracrine regulation of TNF-alpha in m ice toward LPS-treated macrophages under impaired protein synthesis.