Kupffer cells (KC) become activated in response to lipopolysaccharide
(LPS) and produce a variety of mediators. Among them, TNFalpha is know
n to injure the liver. Here we report that TNFalpha mediates apoptosis
in KC and sinusoidal endothelial cells. After stimulation for 24 h wi
th LPS (0-10 mu g/mL), apoptosis in KC detected by TUNEL TdT-mediated
dUTP-biotin nick end labelling (TUNEL) increased in a concentration-de
pendent manner (0 mu g/mL, 12+/-4%; 0.1 mu g/mL, 36+/-11%; 1.0 mu g/mL
, 65+/-9%; 10 mu g/mL, 78+/-15%). In contrast, co-incubation of endoth
elial cells with LPS-stimulated KC resulted in a marked increase in TU
NEL-positive endothelial cells. TNFalpha antibody blocked apoptosis in
both KC and endothelial cells. Apoptosis was observed in cells adjace
nt to or in contact with KC. Reducing transmembrane TNFalpha expressed
on KC also led to a decrease in endothelial cell apoptosis, suggestin
g that transmembrane TNFalpha is implicated in the cell-to-cell contac
t mechanism of induction of apoptosis. Thus, TNFalpha mediates apoptos
is in KC and endothelial cells.