Force-regulated adhesion of leukocytes to vascular surfaces

During inflammation, flowing leukocytes tether to and roll on activated endothelial cells, then decelerate and arrest before they emigrate into the underlying tissues. Interactions of selectins with glycosylated ligands mediate leukocyte rolling, a prerequisite for integrin-mediated deceleration and arrest. Counterintuitively, rolling requires a minimal flow rate, or shear threshold. As flow drops below this threshold, rolling becomes more rapid and irregular until the cells detach. Shear stress applies force to bonds between selectins and their ligands, which affects their lifetimes. As flow increases from suboptimal levels, force first prolongs bond lifetimes (catch bonds) until they reach a maximal level. Further increases in force shorten bond lifetimes (slip bonds). Catch bonds between selectins and ligands enable flow-enhanced adhesion of leukocytes to vascular surfaces and may prevent inappropriate agglutination of circulating cells. Recent data indicate that the mechanical environment of blood flow influences the functions of other adhesion receptors on leukocytes and platelets during infection or tissue injury. Mechanical forces might also regulate migration of tumor cells in extravascular tissues and metastasis of tumor cells through the blood stream.