Mechanisms That Prevent Vascular Leakage During Leukocyte Extravasation

Inflammation is the response of the immune system against harmful stimuli in tissues. Leukocyte extravasation or TransEndothelial Migration (TEM) is a crucial step during inflammation, in which leukocytes migrate over the endothelial barrier toward the damaged tissue.

Historically, it was believed that leukocyte TEM directly causes excessive vascular leakage, resulting in tissue edema. However, it is now clear that leukocyte TEM and vascular leakage are uncoupled events with different spatiotemporal regulation. Moreover, several mechanisms have been identified that prevent vascular leakage during leukocyte TEM.

Here we summarize the different mechanisms that are responsible for limiting the leakage during the transmigration event and explore their clinical relevance in developing targeted therapeutics for controlling vascular leakage in inflammatory diseases.