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Fas ligand expression and apoptosis in primary rat hepatocytes induced by lipopolysaccharide.

OBJECTIVE
To study hepatocyte apoptosis induced by lipopolysaccharide (LPS) directly and indirectly, and to elucidate the mechanisms of liver damage in endotoxemia.


METHODS
Rat hepatocytes were isolated using collagenase perfusion, and cultured in RPMI 1640 medium. After 24h or 48 h of LPS treatment at various concentrations (1, 5, 10 mug/ml), membrane-bound Fas ligand (mFasL) expression in hepatocytes was determined by immunocytochemistry, and apoptosis was detected by TUNEL. In another set of experiments it was examined whether LPS-treated hepatocytes and its supernatants can stimulate apoptosis in LPS-untreated hepatocytes.


RESULTS
LPS markedly stimulated mFasL expression and apoptosis in hepatocytes in a dose and time (24-48 h) dependent manner. In the co-culture system LPS-treated hepatocytes significantly induced LPS-untreated hepatocyte apoptosis. In contrast, there was no apoptotic cells observed in the supernatant stimulation system.


CONCLUSION
LPS not only directly causes hepatocyte apoptosis, but also indirectly induces apoptosis of LPS-untreated hepatocytes by way of stimulating mFasL expression in hepatocytes.