In vivo that intercellular adhesion molecule-1 does not mediate endotoxin-induced hepatic leukocyte-endothelial cell interaction

We have previously demonstrated that endotoxemia induces an immediate leukocytic response within the hepatic microvasculature, with leukostais 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 IgC1 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 systematic leukopenia or intravascular sequestration of leukocytes in endotoxemic livers. Conclusion:Intercellular adhesion molecule-1 does not mediate endotoxin-induced early leukocytic response within hepatic microcirculation.