title: Complement activates Kupffer cells and neutrophils during reperfusion after hepatic ischemia.
abstract: The hypothesis that complement factors may be involved in the postischemic activation of Kupffer cells (KC) and polymorphonuclear neutrophils (PMN) was investigated in a model of hepatic ischemia (45 min) and reperfusion in male Fischer rats in vivo. Depletion of serum complement before ischemia resulted in a significant attenuation of the KC-induced oxidant stress (enhanced oxidation of plasma glutathione) and also prevented the accumulation of PMNs in the liver during the initial reperfusion period of 1 h. Complement activation through injection of cobra venom factor (CVF; 75 micrograms CVF/kg) also induced enhanced oxidation of plasma glutathione and accumulation of PMNs in the liver. Isolation of KC and PMNs from the liver 1 h after CVF treatment demonstrated a similar priming effect for stimulation with phorbol myristate acetate and opsonized zymosan as was observed in the postischemic liver. Complement-depleted animals and animals pretreated with the soluble human complement receptor type 1 (BRL 55730; 22.5 mg/kg) accumulated significantly less PMNs in the postischemic livers during longer reperfusion periods (24 h) and sustained significantly less injury. It is concluded that complement is involved in the induction of a KC-induced oxidant stress, the priming of KC and PMNs for enhanced reactive oxygen generation, and the continuous accumulation of PMNs in the liver during reperfusion.
authors: Department of Medicine, Baylor College of Medicine, Houston 77030.
authors: H
authors: H
authors: Jaeschke
authors: A
authors: A
authors: Farhood
authors: A P
authors: AP
authors: Bautista
authors: Z
authors: Z
authors: Spolarics
authors: J J
authors: JJ
authors: Spitzer
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D003167:Complement Activation / Q000187:drug effects / Q000502:physiology*; D004546:Elapid Venoms / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000097:blood; D019803:Glutathione Disulfide; D007511:Ischemia / Q000503:physiopathology*; D007700:Kinetics; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000098:blood supply* / Q000166:cytology / Q000502:physiology; D008297:Male; D008954:Models, Biological; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D015424:Reperfusion; D015054:Zymosan / Q000494:pharmacology
chemical_list: D004546:Elapid Venoms; C016310:cobra venom factor; D015054:Zymosan; D000410:Alanine Transaminase; D005978:Glutathione; D019803:Glutathione Disulfide