Jaeschke H, Farhood A, Bautista A P, Spolarics Z, Spitzer J J, Smith C W
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Hepatology. 1993 May;17(5):915-23.
The role of neutrophil CD11b/CD18 (Mac-1) adhesion proteins in the pathogenesis of hepatic reperfusion injury was investigated in an experimental model. Male Fischer rats were treated with a CD11b monoclonal antibody or an isotype-matched IgM control antibody and subjected to 45 min of hepatic ischemic followed by 24 hr of reperfusion. Large numbers of neutrophils were present in postischemic liver lobes (1,241 +/- 64 polymorphonuclear cells/50 high-power fields) compared with numbers in baseline measurements (14 +/- 3 polymorphonuclear cells/50 high-power fields), and severe liver injury was observed after 24 hr of reperfusion (hepatic necrosis: 88% +/- 2%). Pretreatment with the CD11b antibody (two doses of 2 mg/kg each significantly attenuated liver injury and reduced the number of polymorphonuclear cells in the post-ischemic liver by 59%. Selective treatment with the antibody only during reperfusion was similarly effective. The increased spontaneous superoxide formation of neutrophils isolated from postischemic liver (1.05 +/- 0.11 nmol O2-/hr/10(6) cells) was reduced by 56% in neutrophils from CD11b antibody-treated animals. Flow cytometric analysis of CD11b/CD18 expression on circulating neutrophils demonstrated significant upregulation at all time points during reperfusion. Clone 17 also effectively inhibited neutrophil extravasation in a glycogen peritonitis model. Our data are consistent with a dual protective effect of the CD11b antibody in hepatic reperfusion injury in vivo (i.e., reduced accumulation of neutrophils and their functional inactivation).
在一个实验模型中研究了中性粒细胞CD11b/CD18（Mac-1）黏附蛋白在肝再灌注损伤发病机制中的作用。雄性Fischer大鼠用CD11b单克隆抗体或同型匹配的IgM对照抗体处理，然后进行45分钟的肝脏缺血，接着再灌注24小时。与基线测量值（14±3个多形核细胞/50个高倍视野）相比，缺血后肝叶中存在大量中性粒细胞（1241±64个多形核细胞/50个高倍视野），并且在再灌注24小时后观察到严重的肝损伤（肝坏死：88%±2%）。用CD11b抗体预处理（每剂2mg/kg，共两剂）可显著减轻肝损伤，并使缺血后肝脏中的多形核细胞数量减少59%。仅在再灌注期间用该抗体进行选择性处理同样有效。从缺血后肝脏分离的中性粒细胞自发超氧化物形成增加（1.05±0.11nmol O2⁻/小时/10⁶个细胞），在接受CD11b抗体处理的动物的中性粒细胞中减少了56%。对循环中性粒细胞上CD11b/CD18表达的流式细胞术分析表明，在再灌注期间的所有时间点均有显著上调。克隆17在糖原性腹膜炎模型中也有效抑制了中性粒细胞外渗。我们的数据与CD11b抗体在体内肝再灌注损伤中的双重保护作用一致（即减少中性粒细胞的积聚及其功能失活）。
