ACTIVATION OF KUPFFER CELLS AND NEUTROPHILS FOR REACTIVE OXYGEN FORMATION IS RESPONSIBLE FOR ENDOTOXIN-ENHANCED LIVER-INJURY AFTER HEPATIC ISCHEMIA
ACTIVATION OF KUPFFER CELLS AND NEUTROPHILS FOR REACTIVE OXYGEN FORMATION IS RESPONSIBLE FOR ENDOTOXIN-ENHANCED LIVER-INJURY AFTER HEPATIC ISCHEMIA
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DOI：
10.1097/00024382-199501000-00010
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发表时间：
1995-01-01
期刊：
影响因子：
3.1
通讯作者：
JAESCHKE, H
中科院分区：
文献类型：
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作者：
LIU, P;MCGUIRE, GM;JAESCHKE, H
在肝缺血后内毒素增强的肝损伤模型中，研究了枯否细胞和中性粒细胞产生的活性氧的潜在作用。使雄性Fischer大鼠经受20分钟缺血和长达24小时的再灌注;在再灌注30分钟时注射0.5mg/kg沙门氏菌内毒素。动物出现严重肝损伤，导致24 h时50%肝细胞坏死。孤立的枯否细胞和中性粒细胞从缺血后的肝脏产生10倍以上的超氧化物比控制肝脏的细胞。用氯化钆（GdCl 3）处理选择性地降低枯否细胞产生超氧化物的能力65%，并在4 h和24 h分别减轻肝损伤73%和58-69%。抗中性粒细胞粘附分子（CD 11/CD 18）的单克隆抗体对早期损伤没有影响，但在24 h时可使肝细胞坏死减少90-95%。抗氧化剂Trolox和铁螯合剂去铁胺分别使肝损伤减轻了71%和80%。结论：Kupffer细胞是早期损伤的主要细胞，而中性粒细胞是晚期的主要细胞毒性细胞类型。由两种细胞类型产生的活性氧对于这种发病机制至关重要。
The potential role of reactive oxygen species generated by Kupffer cells and neutrophils was investigated in a model of endotoxin-enhanced liver injury after hepatic ischemia. Male Fischer rats were subjected to 20 min ischemia and reperfusion of up to 24 h; .5 mg/kg Salmonella enteritidis endotoxin was injected at 30 min of reperfusion. The animals developed severe liver injury resulting in 50% hepatocellular necrosis at 24 h. Isolated Kupffer cells and neutrophils from the postischemic liver generated 10-fold more superoxide than cells from control livers. Treatment with gadolinium chloride (GdCl3) selectively reduced the capacity of Kupffer cells to generate superoxide by 65% and attenuated liver injury by 73% at 4 h and 58-69% at 24 h. Monoclonal antibodies against neutrophil adhesion molecules (CD11/CD18) had no effect on the early injury but reduced hepatocellular necrosis by 90-95% at 24 h. The antioxidant Trolox and the iron-chelator deferoxamine attenuated liver injury by 71 and 80%, respectively. It is concluded that Kupffer cells are mainly responsible for the initial injury, and neutrophils are the dominant cytotoxic cell type during the later phase. Reactive oxygen generated by both cell types is critical for this pathogenesis.