Identification of CD146 as a component of the endothelial junction involved in the control of cell-cell cohesion

CD146 is a cell-surface molecule belonging to the immunoglobulin superfamil y and expressed in all types of human endothelial cells. Confocal and elect ron microscopic analysis of confluent human umbilical vein endothelial cell s (HUVECs) were used to demonstrate that CD146 is a component of the endoth elial junction. Double immunolabeling with vascular endothelial cadherin sh owed that CD146 is localized outside the adherens junction. Moreover, CD146 expression is not restricted to the junction, since part of the labeling w as detectable at the apical side of the HUVECs. Interestingly, cell-surface expression of CD146 increased when HUVECs reached confluence. In addition, the paracellular permeability of CD146-transfected fibroblast cells was de creased compared with that of control cells. Finally, CD146 colocalized wit h actin, was partly resistant to Triton X-100 extraction, and had its expre ssion altered by actin-disrupting agents, indicating that CD146 is associat ed with the actin cytoskeleton. These results show the regulated expression of CD146 at areas of cell-cell junction and strongly suggest involvement o f CD146 as a mediator of cell-cell interaction. (C) 2001 by The American So ciety of Hematology.