Polio Virus Receptor and DNAM1 functionally interact in Transendothelial Migration at a step between PECAM and CD99

Abstract

The movement of leukocytes across the endothelium (referred to as Transendothelial Migration or TEM) is a critical step in the inflammatory process and known to be mediated by PECAM and CD99. Recently Reymond and coworkers showed that Polio Virus Receptor (PVR) on endothelial cells and DNAX‐associated molecule 1 (DNAM1) on monocytes functionally interact to facilitate TEM (J Exp Med, 2004, 199, 1331–41). Having already established that PECAM and CD99 function sequentially in TEM, we sought to determine where PVR and DNAM1 function relative to the activities of PECAM and CD99. We assayed TEM using human endothelial cells and monocytes that had been differentially and sequentially treated with antibodies directed against PVR, DNAM1, PECAM or CD99 that reversibly block TEM. Our findings indicate that endothelial PVR and monocyte DNAM1 interact at a step in between PECAM and CD99. Interestingly, endothelial PVR is protected from extracellular reagents at 4°C, a finding that is consistent with the functional pool of PVR being localized to the lateral border recycling compartment (LBRC) in a fashion similar to PECAM and CD99. This research was supported by F32 AI084454 to DPS and RO1 HL046849 to WAM.