title: The regulation of Fas (CD95/Apo-1)-mediated liver apoptosis in Kupffer cell-depleted mice.
abstract: 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 GdCl(3) 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. GdCl(3) 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.
authors.affiliation: Division of Digestive Diseases and Nutrition, Department of Iinternal Medicine, 800 Rose Street, room N649-0084, University of Kentucky College of Medicine, 40536, Lexington, KY, USA
authors.forename: Ion
authors.initials: I
authors.lastname: Deaciuc
authors.forename: Nympha
authors.initials: N
authors.lastname: D'Souza
authors.forename: Mariana
authors.initials: M
authors.lastname: Nikolova-Karakashian
authors.forename: Willem
authors.initials: W
authors.lastname: de Villiers
authors.forename: Theodore
authors.initials: T
authors.lastname: Sarphie
authors.forename: Daniell
authors.initials: D
authors.lastname: Hill
authors.forename: Craig
authors.initials: C
authors.lastname: McClain