Leukocyte-endothelial cell interactions

Mechanisms that support migration of leukocytes have been studied extensively in vitro. The adhesion of neutrophils under conditions of flow at venous shear rates primarily involves members of the selectin family. E-selectin is upregulated by cytokine stimulation of endothelial cells (ECs); P-selectin is upregulated by stimulation of ECs with agents such as thrombin and histamine; and L-selectin is resident on the surface of unstimulated neutrophils. Each selectin allows neutrophils to roll under conditions of flow. Rolling neutrophils often stop on the EC surface and then rapidly transmigrate. The stationary adhesions and migration are heavily dependent on two members of the CD18 (beta 2) integrin family, CD11a/CD18 and CD11b/CD18, on the neutrophil surface, intercellular adhesion molecule-1 (ICAM-1) on ECs, and endothelial-derived chemoattractants such as interleukin-8 (IL-8). Chemokinetic activation of neutrophils at the endothelial surface induces a transition from selectin-dependent adhesion to CD18/ICAM-1-dependent transmigration that is most clearly evidenced by the shedding of L-selectin from the neutrophil surface and upregulation of CD11b/CD18 to the neutrophil surface.