Leukocyte Breaching of Endothelial Barriers: The Actin Link

Leukocyte transendothelial migration (TEM) takes place across micron-wide gaps in specific post-capillary venules generated by the transmigrating leukocyte. Because endothelial cells contain a dense cytoskeletal network, transmigrating leukocytes must overcome these mechanical barriers as they squeeze their nuclei through endothelial gaps and pores. Recent findings suggest that endothelial cells are not a passive barrier, and upon engagement by transmigrating leukocytes trigger extensive dynamic modifications of their actin cytoskeleton. Unexpectedly, endothelial contractility functions as a restrictor of endothelial gap enlargement rather than as a facilitator of gap formation as was previously suggested. In this review we discuss current knowledge regarding how accurately timed endothelial actin-remodeling events are triggered by squeezing leukocytes and coordinate leukocyte TEM while preserving blood vessel integrity.