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Role of polymorphonuclear leukocytes in galactosamine hepatitis: Mechanism of adherence to hepatic endothelial cells
Author(s) -
Komatsu Yutaka,
Shiratori Yasushi,
Kawase Tateo,
Hashimoto Naoaki,
Han Katsuken,
Shiina Shuichiro,
Matsumura Masayuki,
Niwa Yasuro,
Kato Naoya,
Tada Minoru,
Ikeda Yusei,
Tanaka Mitsugu,
Omata Masao
Publication year - 1994
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840200626
Subject(s) - galactosamine , lipopolysaccharide , tumor necrosis factor alpha , intercellular adhesion molecule 1 , superoxide , cell adhesion molecule , inflammation , immunology , granulocyte , medicine , chemistry , biochemistry , enzyme , glucosamine
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‐α 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‐α. In addition, prostaglandins E 1 and E 2 lessened the enhanced adherence of polymorphonuclear leukocytes and thus contributed to protection against hepatic injury. (Hepatology 1994;20:1548–1556).