ROLE OF CD11/CD18 IN SHEAR RATE-DEPENDENT LEUKOCYTE-ENDOTHELIAL CELL-INTERACTIONS IN CAT MESENTERIC VENULES

In vivo microscopy was used to assess the relationships among shear rate (and shear stress), leukocyte rolling velocity, and leukocyte adherence in a cat mesentery preparation. Shear rate in individual venules and arterioles of 25-35-mu-m diameter were varied over a wide range by graded occlusion of an arterial loop. There was a linear decline in leukocyte rolling velocity (V(wbc)) as red cell velocity (V(rbc)) was reduced. The ratio V(wbc)/V(rbc) remained constant despite variations in shear stress from 5-25 dyn/cm2. A reduction in shear stress was associated with an increased leukocyte adherence, particularly when V(wbc) was reduced below 50-mu-m/s. Reduction in wall shear rate below 500 s-1 in arterioles allowed 1-3 leukocytes to adhere per 100-mu-m length of vessel, while venules exposed to the same shear rates had 5-16 adherent leukocytes. In arterioles, leukocyte rolling was only observed at low shear rates. At shear rates < 250 s-1 leukocyte rolling velocity was faster in arterioles than venules, and the ratio V(wbc)/V(rbc) for arterioles was 0.08 +/- 0.02, which was fourfold higher than the ratio obtained in venules at similar shear rates. Pretreatment with the CD18-specific antibody (mAb) IB4 increased leukocyte rolling velocity in venules by approximately 20-mu-m/s at red cell velocities below 2,000-mu-m/s.mAb IB4 largely prevented the leukocyte adherence to arterioles and venules, and increased the ratio V(wbc)/V(rbc) observed in venules at low shear rates. The results of this study indicate that low shear rates elicit a CD18-dependent adhesive interaction between leukocytes and microvascular endothelium, and that differences in shear rates cannot explain the greater propensity for leukocyte rolling and adhesion in venules than arterioles.