Complement activates Kupffer cells and neutrophils during reperfusion after hepatic ischemia.
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.
Jaeschke
H
H
Department of Medicine, Baylor College of Medicine, Houston 77030.
Farhood
A
A
Bautista
A P
AP
Spolarics
Z
Z
Spitzer
J J
JJ
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
D004546:Elapid Venoms; C016310:cobra venom factor; D015054:Zymosan; D000410:Alanine Transaminase; D005978:Glutathione; D019803:Glutathione Disulfide