Cytomegalovirus-induced transendothelial cell migration - A closer look atintercellular communication mechanisms

A variety of cells such as leukocytes and tumor cells may adhere to endothe lial cells and subsequently transmigrate into the solid tissue by involving specific intercellular molecular pathways. One important prerequisite for transendothelial migration is the loosening of endothelial cell-to-cell con tact sites, which can be triggered by extravasating cells. Cytomegalovirus (CMV) has obviously evolved the ability not only to influence host cells fl oating in the blood stream to adhere to endothelial cells, but also to indu ce the formation of intercellular gaps within the endothelium, resulting in transendothelial migration. These features allow the virus to disseminate and evade the immune system. In coculture experiments with human endothelia l monolayers and human CMV (HCMV)-infected neuroblastoma cells or leukocyte s, changes in the integrity of the monolayer were observed and further anal yzed on the molecular level. For example, HCMV may activate the integrin be ta 1 alpha 5 (VLA-5) that triggers adhesion to endothelial cells with subse quent focal disruption of endothelial cell-to-cell connections. It is hypot hesized that a Ca2+-independent pathway following VLA-5 binding disconnects the cadherin-catenin-actin complex within the endothelial cells. The loss of cadherin function causes the loss of contact to the neighboring endothel ial cells and thus could represent an important mechanism in HCMV-induced c ellular transendothelial migration and disruption of the endothelial integr ity. Copyright (C) 2000 S. Karger AG, Basel.