Leukocyte Extravasation Signaling

Leukocyte extravasation is the process by which leukocytes migrate from blood to tissue during inflammation. It occurs in a series of steps:1)capture and rolling - Capture or tethering represents the first contact between an endothelial cell and leukocyte. It is mediated by P/E-SELECTIN on endothelial cells that binds to ligands like PSGL-1 on leukocytes. Capture is followed by rolling where bonds are formed at the leading edge of the rolling cell and broken at the trailing edge. PSGL-1 is involved in rolling through its interacts with members of the ERM family. ERM proteins link the plasma membrane with the actin cytoskeleton.2)slow rolling and firm adhesion - chemokines secreted by macrophages and endothelial cells activate leukocytes and cause surface integrins to change from a low affinity to a high affinity state. For example, neutrophil adhesion is mediated by high affinity state beta2-integrin, LFA-1, binding to ICAM-1. Tight binding allows the firm adhesion of leukocytes to the endothelium despite shear forces of blood flow in the blood vessel.3)transmigration - this is the process where leukocytes, with the help of pseudopodia, migrate through spaces between endothelial cells. JAMs and PECAMs are transmembrane proteins on the surface of leukocytes that act sequentially to mediate transmigration. Leukocytes secrete proteases like MMP-9 to degrade the basement membrane and finally allow the leukocyte to enter interstial spaces in tissue.