Selectin-dependent leukocyte interactions with vascular surfaces

Binding of selectins to cell-surface ligands mediates rolling of leukocytes on activated platelets and endothelial cells and on other leukocytes. These multicellular adhesive interactions contribute to immune surveillance and to responses to tissue injury and infection. The leukocyte mucin, P-selectin glycoprotein ligand-1 (PSGL-1), mediates interactions with L-selectin on other leukocytes and with P-selectin on activated platelets and endothelial cells. Both molecular and cellular features affect selectin-dependent rolling under flow. One important cellular feature is the extrusion of long, thin membrane tethers, which reduce force on adhesive bonds and increase the probability of forming additional bonds along the tether. The kinetic and mechanical properties of selectin-ligand interactions also modulate rolling. At low force regimes, increasing wall shear stress prolongs the lifetimes of bonds between PSGL-1 and either P-selectin or L-selectin; these counter-intuitive interactions are called catch bonds. Further increases in wall shear stress shorten lifetimes; these interactions are called slip bonds. Stabilization of catch bonds may account for the shear threshold requirement for L-selectin-dependent rolling.