PMID: 8589347Jan 1, 1995Paper

Apoptosis: a new mechanism of endothelial and Kupffer cell killing

Journal of Gastroenterology and Hepatology
Y TakeiK Ikeda

Abstract

Kupffer cells (KC) become activated in response to lipopolysaccharide (LPS) and produce a variety of mediators. Among them, TNF alpha is known to injure the liver. Here we report that TNF alpha mediates apoptosis in KC and sinusoidal endothelial cells. After stimulation for 24 h with LPS (0-10 micrograms/mL), apoptosis in KC detected by TUNEL TdT-mediated dUTP-biotin nick end labelling (TUNEL) increased in a concentration-dependent manner (0 micrograms/mL, 12 +/- 4%; 0.1 microgram/mL, 36 +/- 11%; 1.0 micrograms/mL, 65 +/- 9%; 10 micrograms/mL, 78 +/- 15%). In contrast, co-incubation of endothelial cells with LPS-stimulated KC resulted in a marked increase in TUNEL-positive endothelial cells. TNF alpha antibody blocked apoptosis in both KC and endothelial cells. Apoptosis was observed in cells adjacent to or in contact with KC. Reducing transmembrane TNF alpha expressed on KC also led to a decrease in endothelial cell apoptosis, suggesting that transmembrane TNF alpha is implicated in the cell-to-cell contact mechanism of induction of apoptosis. Thus, TNF alpha mediates apoptosis in KC and endothelial cells.

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Citations

Aug 15, 2002·Journal of Hepatology·Jung-Hwan Yoon, Gregory J Gores
Oct 7, 2009·Pharmacological Reviews·Xiaomin DengRobert A Roth
Jan 7, 1998·The Journal of Experimental Medicine·A Haimovitz-FriedmanR Kolesnick
Jan 13, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·M MüschenD Häussinger
Dec 17, 2009·Pathology·Rajkumar CheluvappaDavid G Le Couteur
Jul 9, 2010·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Rajkumar CheluvappaDavid G Le Couteur
Aug 19, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Francis F TukovRobert A Roth
Jul 29, 2009·International Journal of Cancer. Journal International Du Cancer·Takashi SakaiKiyoshi Fukui
May 22, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Natalia CuestaStefanie N Vogel
Jul 1, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G A WannerW Ertel

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis