The regulation of Fas (CD95/Apo-1)-mediated liver apoptosis in Kupffer cell-depleted mice

被引:9
作者
Deaciuc, IV
D'Souza, NB
Nikolova-Karakashian, M
de Villiers, WJS
Sarphie, TG
Hill, DB
McClain, CJ
机构
[1] Univ Kentucky, Coll Med, Dept Internal Med, Div Digest Dis & Nutr, Lexington, KY 40536 USA
[2] Univ Kentucky, Coll Med, Dept Internal Med, Div Pulm Crit Care, Lexington, KY 40536 USA
[3] Univ Kentucky, Coll Med, Dept Physiol, Lexington, KY 40536 USA
[4] Louisiana State Univ, Hlth Sci Ctr, Dept Anat & Cell Biol, New Orleans, LA 70112 USA
[5] Univ Louisville, Dept Internal Med, Div Gastroenterol Hepatol, Louisville, KY 40292 USA
[6] Vet Adm Med Ctr, Louisville, KY 40292 USA
关键词
anti-apoptotic regulators; pro-apoptotic regulators; gadolinium chloride; glutathione;
D O I
10.1016/S1386-6346(02)00021-9
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The purpose of this study was to further characterize Fas-mediated liver apoptosis. We investigated whether Fas-mediated apoptosis in the liver requires induction of apoptosis-related regulators and whether Kupffer cells play a role in this process. Mice were injected with GdCl3 to deplete/suppress Kupffer cells, followed by treatment with an anti-Fas agonistic antibody, Jo2. Hepatic mRNA levels of several pro- and anti-apoptotic regulators were determined 0.5, 1.5 and 4.0 h after Jo2 injection. Liver histology, TUNEL response, the activity of caspases-3, -8, and -9, and reduced and oxidized glutathione, were also evaluated. Jo2 dramatically increased the number of apoptotic nuclei in the liver, up-regulated mRNA for Bcl-w, Bfl-1, and Bcl-X-L, but did not affect pro-apoptotic regulator mRNA expression. Caspase-3, -8 and -9 activity increased at 1.5 h after Jo2-injection. GdCl3 treatment was associated with an increase in the apoptotic effect of Jo2. No effect of Jo2 was recorded on redox state of the free cellular thiol system. These data suggest that: (1) the prompt apoptotic response to Fas-mediated signaling in the liver does not require induction of pro-apoptotic factors; (2) Kupffer cells may play a major role in the liver apoptotic response to Fas ligation by clearing apoptotic cells by phagocytosis; (3) oxidative stress does not seem to play an important role in Fas-mediated liver apoptosis. (C) 2002 Published by Elsevier Science B.V.
引用
收藏
页码:192 / 204
页数:13
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