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Apoptosis: A new mechanism of endothelial and Kupffer cell killing
Author(s) -
TAKEI YOSHIYUKI,
KAWANO SUNAO,
NISHIMURA YOSHIYA,
GOTO MORITAKA,
NAGAI HIROTAKA,
CHEN SHENGSONG,
OMAE ATSUSHI,
FUSAMOTO HIDEYUKI,
KAMADA TAKENOBU,
IKEDA KAZUO,
KAWADA NORIFUMI,
KANEDA KENJI
Publication year - 1995
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.1995.tb01802.x
Subject(s) - medicine , apoptosis , mechanism (biology) , microbiology and biotechnology , cancer research , endothelial stem cell , immunology , genetics , epistemology , biology , in vitro , philosophy
Kupffer cells (KC) become activated in response to lipopolysaccharide (LPS) and produce a variety of mediators. Among them, TNFα is known to injure the liver. Here we report that TNFα mediates apoptosis in KC and sinusoidal endothelial cells. After stimulation for 24 h with LPS (0‐10 μg/mL), apoptosis in KC detected by TUNEL TdT‐mediated dUTP‐biotin nick end labelling (TUNEL) increased in a concentration‐dependent manner (0 μg/mL, 12 ± 4%; 0.1 μg/mL, 36 ± 11%; 1.0 μg/mL, 65 ± 9%; 10 μg/mL, 78 ± 15%). In contrast, co‐incubation of endothelial cells with LPS‐stimulated KC resulted in a marked increase in TUNEL‐positive endothelial cells. TNFα antibody blocked apoptosis in both KC and endothelial cells. Apoptosis was observed in cells adjacent to or in contact with KC. Reducing transmembrane TNFα expressed on KC also led to a decrease in endothelial cell apoptosis, suggesting that transmembrane TNFα is implicated in the cell‐to‐cell contact mechanism of induction of apoptosis. Thus, TNFα mediates apoptosis in KC and endothelial cells.