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Reductions in physiologic shear rates lead to CD11/CD18-dependent,
selectin-independent leukocyte rolling in vivo
JP Gaboury and P Kubes
Department of Medical Physiology, University of Calgary, Alberta, Canada.
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.
Volume 83,
Issue 2,
pp. 345-350,
01/15/1994
Copyright © 1994 by The American Society of Hematology
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