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Role of adhesion molecules in the development of massive hepatic necrosis in rats
Author(s) -
Mochida S,
Ohno A,
Arai M,
Tamatani T,
Miyasaka M,
Fujiwara K
Publication year - 1996
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.510230219
Subject(s) - necrosis , cell adhesion molecule , intercellular adhesion molecule 1 , liver injury , tumor necrosis factor alpha , icam 1 , monoclonal antibody , pathology , hepatic stellate cell , propionibacterium acnes , endothelial stem cell , lymphocyte function associated antigen 1 , immunology , antibody , biology , medicine , endocrinology , biochemistry , in vitro , genetics , bacteria
Massive hepatic necrosis develops after endotoxin administration in rats pretreated with heat‐killed Propionibacterium acnes as a result of microcirculatory disturbance caused by endothelial cell destruction by activated macrophages in the hepatic sinusoids. Immunohistochemical hepatic expression of intercellular adhesion molecule‐1 (ICAM‐1) and lymphocyte function‐associated antigen 1 α (LFA‐1 α) and the effect of monoclonal antibodies against both adhesion molecules on liver necrosis provoked after endotoxin administration was studied in these rats. There were increased stains of ICAM‐1 in endothelial cells and LFA‐1 α in macrophages in the hepatic sinusoids in Propionibacterium acnes ‐pretreated rats compared with normal rats. Such stains were further increased soon after endotoxin administration, followed by development of hepatic necrosis. Monoclonal antibodies against both adhesion molecules significantly attenuated the extent of liver injury compared with controls, without affecting the infiltration and activation of hepatic macrophages. Polyclonal antibodies against polymorphonuclear leukocytes eradicated circulating neutrophils, but did not change such liver injury, although gum arabic, which suppressed macrophage activation, attenuated the extent of liver injury. Thus, adhesion between endothelial cells and activated macrophages in the hepatic sinusoids via ICAM‐1 and LFA‐1 α is essential for the initiation of massive hepatic necrosis of this type. Contribution of neutrophils seems less likely.