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In vivo evidence that intercellular adhesion molecule-1 does not mediate endotoxin-induced hepatic
B Vollmar1, A Senkel, M D Menger
1Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
Background/Aims:
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.