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.
Harris
N R
NR
Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport 71130-3932.
Russell
J M
JM
Granger
D N
DN
D000818:Animals; D000911:Antibodies, Monoclonal; D001381:Azepines / Q000494:pharmacology; D018845:CD11 Antigens / Q000502:physiology; D018821:CD18 Antigens / Q000502:physiology; D002415:Cats; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D004731:Endotoxins / Q000633:toxicity*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008643:Mesentery / Q000098:blood supply* / Q000166:cytology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013482:Superoxide Dismutase / Q000502:physiology; D014230:Triazoles / Q000494:pharmacology; D014699:Venules / Q000166:cytology*
D000911:Antibodies, Monoclonal; D001381:Azepines; D018845:CD11 Antigens; D018821:CD18 Antigens; D004731:Endotoxins; D008070:Lipopolysaccharides; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; D018799:Intercellular Adhesion Molecule-1; C044101:endotoxin, Escherichia coli; D013482:Superoxide Dismutase