Molecular determinants of shear rate-dependent leukocyte adhesion in postcapillary venules

Abstract

Recent studies have demonstrated that reductions in shear rate are associated with the recruitment of rolling and adherent leukocytes in postcapillary venules. The objective of this study was to define the molecular determinants of the leukocyte-endothelial cell adhesive interactions elicited by low venular shear rates. Three different monoclonal antibodies (MAb) were used to assess the relative contributions of CD18 (MAb R15.7), intercellular adhesion molecule 1 (ICAM-1; MAb RR1/1), and P-selectin (MAb PB1.3) to shear rate-dependent leukocyte rolling and adherence. Erythrocyte velocity, vessel diameter, leukocyte adherence, and leukocyte rolling velocity were monitored in cat mesenteric venules (25-40 microns diam). Venular shear rate was varied in a stepwise fashion by graded occlusion of an arterial circuit between the femoral and superior mesenteric arteries. Shear rates were maintained at each level for a period of 2 min. The MAbs directed against either CD18 or ICAM-1, but not P-selectin, significantly attenuated the recruitment of adherent leukocytes normally observed at low shear rates. However, the MAb against P-selectin, but not CD18 or ICAM-1, was effective in reducing the recruitment of rolling leukocytes elicited by low shear rates. These observations indicate that shear rate-dependent recruitment of adherent leukocytes involves an interaction between CD11/CD18 on leukocytes and ICAM-1 on vascular endothelium, while P-selectin on endothelial cells mediates, at least part of, the recruitment of rolling leukocytes.