In vivo evidence that intercellular adhesion molecule-1 does not mediate endotoxin-induced hepatic leukocyte-endothelial cell interaction.
OBJECTIVE
We have previously demonstrated that endotoxemia induces an immediate leukocytic response within the hepatic microvasculature, with leukostasis in sinusoids and leukocyte adherence in post-sinusoidal venules. We have now studied the role of intercellular adhesion molecule-1 in endotoxin-induced hepatic leukocyte-endothelial cell interaction in vivo using fluorescence microscopy.


METHODS
Sprague-Dawley rats were pretreated with either 1 mg/kg (n = 5) or 2 mg/kg (n = 4) of a monoclonal anti-rat anti-intercellular adhesion molecule-1 antibody intravenously, followed by exposure to endotoxin (E. coli LPS 10 mg/kg iv). Animals pretreated with an isotype-matched IgG1 control antibody (n = 5) served as controls. Intravital fluorescence microscopy for analysis of the hepatic microcirculation was performed prior to and 1 h after lipopolysaccharide exposure.


RESULTS
At 1 h after lipopolysaccharide-exposure, control animals showed a marked reduction of systemic leukocyte count, which was associated with a significant (p < 0.01) hepatic microvascular accumulation of leukocytes with stasis in sinusoids, as well as rolling and adherence in postsinusoidal venules. Pretreatment with anti-intercellular adhesion molecule-1 was not effective in preventing either systemic leukopenia or intravascular sequestration of leukocytes in endotoxemic livers.


CONCLUSIONS
Intercellular adhesion molecule-1 does not mediate endotoxin-induced early leukocytic response within the hepatic microcirculation.
Vollmar
B
B
Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
Senkel
A
A
Menger
M D
MD
D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D008070:Lipopolysaccharides; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008856:Microscopy, Fluorescence; D051381:Rats; D017207:Rats, Sprague-Dawley
D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1