Leukocyte rolling velocity and its relation to leukocyte-endothelium adhesion and cell deformability

To explore the relationship between the rolling velocity of leukocytes (V(WBC)) and wall shear rates (γ̇), measurements of V(WBC) were made along the length of rat mesenteric venules in which a gradient in γ̇ was induced by compressing the venule with a blunted microprobe to form a stenosis in which γ̇ varied from 300 to 1500 s^-1. For individual WBCs that rolled through the stenosis, V(WBC) was proportional to γ̇ its entire range, in contrast to previous studies that have shown a plateau in V(WBC) vs. γ̇ for the ensemble population. Comparisons of the slope of V(WBC) vs. γ̇ for individual cells with ensemble values of V(WBC)/γ̇ obtained in the entrance region of the stenosis were made during suffusion of the tissue with the chemoattractant N-formylmethionyl-leucyl-phenylalanine (FMLP), to increase WBC-EC adhesion and WBC stiffness, or colchicine and cytochalasin B to increase WBC deformability. Under control conditions, the slope of individual cells was significantly 20% greater than V(WBC)/γ̇, whereas it was significantly reduced by 48% during suffusion with FMLP. With exposure to colchicine, the slope was 78% lower than V(WBC)/γ̇ and compared with control was similar in magnitude to that obtained with FMLP. Cytochalasin also reduced the slope by 22% compared with control and 34% compared with V(WBC)/γ̇. The diminished slopes of V(WBC) vs. γ̇ were consistent with published theoretical models that suggest a reduced slope with increased strength of adhesion or WBC deformability. It is thus concluded that the apparent plateau in V(WBC) vs γ̇ arises due to the heterogeneity of adhesive and/or deformability properties of the ensemble population of circulating WBCs.