and restores Kupffer cell clearance capacity. FASEB J. 13, 1239â1248 (1999). Key Words: liver failure apoptosis hepatic microcirculation cysteine protease.
Inhibition of caspase activity prevents CD95-mediated hepatic microvascular perfusion failure and restores Kupffer cell clearance capacity GUIDO A. WANNER,* LADISLAV MICA,* ELISABETH WANNER-SCHMID,* STEFAN A. KOLB,† HANNES HENTZE,‡ OTMAR TRENTZ,* AND WOLFGANG ERTEL*,1 *Division of Trauma Surgery and †Department of Pathology, University Hospital Zurich, CH-8091 Zurich, Switzerland; and ‡Department of Biochemical Pharmacology, University of Konstanz, D-78457 Konstanz, Germany ABSTRACT Using a murine model, we studied the effect of agonistic anti-CD95 antibodies (aCD95) on sinusoidal lining cells and a potential protection by caspase inhibition. C3H/HeN mice were intravenously administered aCD95 (10 mg/mouse) or unspecific IgG (control) in the presence or absence of the caspase inhibitor z-VAD-fmk. Analysis of hepatic microcirculation using intravital fluorescence microscopy revealed severe (P
