Release of soluble intercellular adhesion molecule 1 into bile and serum in murine endotoxin shock.
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 micrograms/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 alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) or IL-1 beta (13-23 micrograms/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.
Jaeschke
H
H
Cardiovascular Pharmacology, Pharmacia & Upjohn Inc., Kalamazoo, MI 49001, USA.
Essani
N A
NA
Fisher
M A
MA
Vonderfecht
S L
SL
Farhood
A
A
Smith
C W
CW
D000704:Analysis of Variance; D000818:Animals; D001646:Bile / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D004731:Endotoxins / Q000097:blood*; D005688:Galactosamine / Q000633:toxicity; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012772:Shock, Septic / Q000276:immunology* / Q000378:metabolism; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004731:Endotoxins; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D005688:Galactosamine