Leukocyte transendothelial migration hotspots at a glance.

Leukocytes traverse the vasculature to reach sites of infection by sequentially crossing two distinct barriers - the endothelial barrier, during transendothelial migration (TEM), and the pericyte barrier, during trans-pericyte migration (TPM). Emerging evidence has underscored that TEM and TPM do not occur randomly but are confined to specialized 'hotspot' regions. This Cell Science at a Glance article and the accompanying poster overview the mechanisms underlying the heterogeneity within the inflamed endothelial monolayer, as well as within the perivascular cells, that defines these hotspots, highlighting how leukocytes themselves can actively induce new hotspots during the extravasation process. Furthermore, we explore the diverse mechanisms governing the production, storage and presentation of chemokines during extravasation. Finally, we elucidate the regulatory strategies employed by endothelial cells to maintain vascular integrity and prevent leakage during leukocyte transmigration, collectively offering a comprehensive perspective on the intricate interactions between leukocytes and (peri)vascular cells during immune cell extravasation.