Reductions in physiologic shear rates lead to CD11/CD18-dependent, selectin-independent leukocyte rolling in vivo.
In this study, we tested the hypothesis that reducing shear rates in postcapillary venules causes CD18-dependent, selectin-independent leukocyte rolling. Intravital microscopy was used to assess shear rate-dependent leukocyte rolling in 25- to 40-microns rat mesenteric venules. Pretreatment of animals with 25 mg/kg fucoidin, a carbohydrate moiety that binds to and inhibits selectin function, essentially abolished the number of spontaneously rolling leukocytes. When shear rates were reduced by 50% (from 438 +/- 36 s-1 to 222 +/- 19 s-1) in the presence of fucoidin, leukocyte rolling increased fourfold, suggesting a selectin-independent mechanism of leukocyte rolling. Administration of CL26, an anti-CD18 antibody, prevented the leukocyte rolling associated with reduced shear rates. A second objective was to determine if the integrin-mediated leukocyte rolling at reduced shear rates would lead to firm adhesion of leukocytes in the presence of a chemotactic stimulus. Animals were pretreated with fucoidin and 100 nmol/L platelet-activating factor (PAF) was superfused over the mesentery. Fucoidin prevented leukocyte rolling and subsequent PAF-induced adhesion at normal shear rates; however, when shear rates were reduced by 50%, a significant CD18-dependent increase in leukocyte rolling (10-fold) and adhesion (5-fold) was noted within 15 minutes. These data raise the possibility that, at lower shear rates, as is the case in various inflammatory conditions, selectin-independent, CD18-dependent leukocyte rolling and subsequent adhesion can occur in postcapillary venules.
Gaboury
J P
JP
Department of Medical Physiology, University of Calgary, Alberta, Canada.
Kubes
P
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology*; D001696:Biomechanical Phenomena; D018845:CD11 Antigens; D018821:CD18 Antigens; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D019041:L-Selectin; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D019007:P-Selectin; D010972:Platelet Activating Factor / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D011134:Polysaccharides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D019007:P-Selectin; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011134:Polysaccharides; D019041:L-Selectin; C007789:fucoidan