An inconvenient truth: Leukocyte transendothelial migration without PECAM

Leukocyte transendothelial migration (TEM), the process by which leukocytes leave the circulation, cross the endothelial barrier, and enter tissue to engage in effector functions, is a multistep process involving a number of different intercellular adhesion molecules. Diapedesis, the committed step of TEM, during which the leukocyte actually squeezes between endothelial cells, is known to involve at least two distinct steps, mediated by the Platelet/Endothelial Cell Adhesion Molecule (PECAM) and CD99. In the studies detailed herein, we have taken several approaches to characterizing additional molecules involved in diapedesis. Our first study uses molecular genetics in the laboratory mouse to identify a locus on mouse chromosome 2 that is apparently responsible for the ability of C57BL/6J mice to show a robust inflammatory response to thioglycollate broth even when PECAM is functionally blocked or genetically deficient. Our second study uses an in vitro model of TEM to demonstrate that prostaglandin E2 is capable of reversing the blockade in TEM seen when PECAM is inhibited. Our third study uses the same in vitro system to characterize a potentially novel step in diapedesis mediated by the molecules DNAX Accessory Molecule 1 (DNAM-1) and the Poliovirus Receptor (PVR).