Komatsu Y, Shiratori Y, Kawase T, Hashimoto N, Han K, Shiina S, Matsumura M, Niwa Y, Kato N, Tada M
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Hepatology. 1994 Dec;20(6):1548-56. doi: 10.1002/hep.1840200626.
To investigate the role of polymorphonuclear leukocytes in galactosamine-induced hepatic injury, we injected rats intraperitoneally with antiserum against rat polymorphonuclear leukocytes to deplete circulating neutrophils, then administered galactosamine plus lipopolysaccharide. Polymorphonuclear leukocytes in the hepatic sinusoids were increased after administration of galactosamine plus lipopolysaccharide, whereas pretreatment with the antiserum decreased the number of circulating leukocytes and reduced the mortality and the severity of hepatic injury. Serum collected 1 hr after galactosamine/lipopolysaccharide treatment enhanced in vitro polymorphonuclear leukocyte adherence to hepatic endothelial cells and induced leukocyte superoxide production. Intercellular adhesion molecule-1 expression on hepatic endothelial cells was also enhanced after stimulation with the serum. Polymorphonuclear leukocyte adhesion was partially inhibited by an antibody against tumor necrosis factor-alpha but not by superoxide dismutase. These results suggest that polymorphonuclear leukocytes play an important role in galactosamine-induced hepatic injury and that the accumulation and activation of leukocytes, as well as the enhanced expression of adhesion molecules on hepatic endothelial cells, can be induced by biologically active mediators such as tumor necrosis factor-alpha. In addition, prostaglandins E1 and E2 lessened the enhanced adherence of polymorphonuclear leukocytes and thus contributed to protection against hepatic injury.
为了研究多形核白细胞在半乳糖胺诱导的肝损伤中的作用，我们给大鼠腹腔注射抗大鼠多形核白细胞抗血清以耗尽循环中的中性粒细胞，然后给予半乳糖胺加脂多糖。给予半乳糖胺加脂多糖后，肝血窦中的多形核白细胞增加，而用抗血清预处理可减少循环白细胞数量，并降低死亡率和肝损伤的严重程度。半乳糖胺/脂多糖处理1小时后收集的血清增强了体外多形核白细胞对肝内皮细胞的黏附，并诱导白细胞产生超氧化物。用该血清刺激后，肝内皮细胞上细胞间黏附分子-1的表达也增强。多形核白细胞黏附被抗肿瘤坏死因子-α抗体部分抑制，但不被超氧化物歧化酶抑制。这些结果表明，多形核白细胞在半乳糖胺诱导的肝损伤中起重要作用，并且白细胞的积聚和激活以及肝内皮细胞上黏附分子表达的增强可由肿瘤坏死因子-α等生物活性介质诱导。此外，前列腺素E1和E2减少了多形核白细胞增强的黏附，从而有助于预防肝损伤。
