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Release of soluble intercellular adhesion molecule 1 into bile and serum in murine endotoxin shock
Author(s) -
Jaeschke H,
Essani N A,
Fisher M A,
Vonderfecht S L,
Farhood A,
Smith C W
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.510230318
Subject(s) - intracellular , adhesion , chemistry , intercellular adhesion molecule 1 , shock (circulatory) , biochemistry , medicine , organic chemistry
Neutrophil‐induced liver injury during endotoxemia is dependent on the adhesion molecules Mac‐1 (CD11b/CD18) on neutrophils and its counterreceptor on endothelial cells and hepatocytes, intercellular adhesion molecule 1 (ICAM‐1). To investigate a potential release of a soluble form of ICAM‐1 (sICAM‐1), animals received 100 μg/kg Salmonella abortus equi endotoxin alone or in combination with 700 mg/kg galactosamine. In endotoxin‐sensitive mice (C3Heb/FeJ), injection of endotoxin did not cause liver injury but induced a time‐dependent increase of sICAM‐1 in serum (300%) and in bile (615%) without affecting bile flow. In galactosamine/endotoxin‐treated animals, which developed liver injury, the increase in both compartments was only 97% and 104%, respectively. In either case, the increase in sICAM‐1 concentrations paralleled the enhanced ICAM‐1 expression in the liver. The endotoxin‐resistant strain (C3H/HeJ) did not show elevated sICAM‐1 levels in serum or bile after endotoxin administration. In contrast, the intravenous injection of murine tumor necrosis factor α (TNF‐α), interleukin‐1α (IL‐1α) or IL‐1β (13‐23 μg/kg) into endotoxin‐resistant mice induced a 225% to 364% increase in serum sICAM‐1 and a 370% elevation of the biliary efflux of sICAM‐1, again independent of changes in bile flow. These data indicate that cytokines are major inducers of sICAM‐1 formation during endotoxemia in vivo . The described experimental model can be used to investigate the role of sICAM‐1 in the pathophysiology of inflammatory liver disease.