Threshold levels of fluid shear promote leukocyte adhesion through selectins (CD62L,P,E)

Leukocyte adhesion through L-selectin to MECA-79 antigen, an L-selectin ligand expressed on high endothelial venules, has been shown to require a minimum level of fluid shear stress (Finger et al. Nature 379:266-269). Fluid shear above a threshold of 0.5 dyn/cm² wall shear stress also significantly enhances HL-60 cells rolling on P-selectin and E-selectin at site densities of 200/μm² and below. In addition, gravitational force is sufficient to detach HL-60 cells from P-selectin and E-selectin substrates in the absence, but not in the presence of flow, suggesting that fluid shear-induced torque is critical for the maintenance of leukocyte rolling. Murine 300.19 cells transfected with L-selectin failed to roll on MECA-79 antigen at wall shear stresses below 0.5 dyn/cm². Similarly, K562 cells transfected with PSGL-1, a ligand for P-selectin, showed a reduction in rolling on P-selectin below this level of wall shear stress. Leukocyte rolling flux fraction as assessed by intravital microscopy of cremaster muscle venules was reduced at blood centerline velocities less than 1 mm/s in a model in which rolling is mediated by L-selectin and P-selectin. Similar observations were made in L-selectin deficient mice in which leukocyte rolling is entirely P-selectin dependent. Leukocyte adhesion through all three selectins appears to be significantly enhanced by a threshold level of fluid shear stress.