Mediators of endotoxin-induced leukocyte adhesion in mesenteric postcapillary venules

Intravital video microscopy was used to monitor and quantify leukocyte-endothelial cell adherence, leukocyte emigration, venular shear rate, and leukocyte rolling velocity in cat mesenteric venules exposed to E. coli endotoxin lipopolysaccharides (LPS). LPS induced a steady decrease in venular shear rate and leukocyte rolling velocity while increasing leukocyte adherence and emigration. The molecular determinants and chemical mediators of LPS-induced leukocyte-endothelial cell adhesion were investigated using monoclonal antibodies (MAbs) against the adhesion glycoproteins CD11/CD18 on leukocytes (MAb IB4) and ICAM-1 (MAb RR1/1) on endothelial cells as well as superoxide dismutase (SOD) and a platelet-activating factor receptor antagonist (WEB 2086). Leukocyte adherence was significantly (P < .05) reduced by administration of either the CD11/CD18 MAb or SOD, while the PAF receptor antagonist and ICAM-1 MAb had no effect. None of the four agents studied significantly altered LPS-induced leukocyte emigration, venular shear rate, or leukocyte rolling velocity. These results indicate that the leukocyte adherence induced by LPS is dependent on the adhesion glycoprotein CD11/CD18 and superoxide, and that an endothelial cell ligand other than ICAM-1 participates in this adhesion process.