Cytomegalovirus-induced transendothelial cell migration. a closer look at intercellular communication mechanisms.
A variety of cells such as leukocytes and tumor cells may adhere to endothelial 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 contact sites, which can be triggered by extravasating cells. Cytomegalovirus (CMV) has obviously evolved the ability not only to influence host cells floating in the blood stream to adhere to endothelial cells, but also to induce 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 endothelial monolayers and human CMV (HCMV)-infected neuroblastoma cells or leukocytes, changes in the integrity of the monolayer were observed and further analyzed on the molecular level. For example, HCMV may activate the integrin beta1alpha5 (VLA-5) that triggers adhesion to endothelial cells with subsequent focal disruption of endothelial cell-to-cell connections. It is hypothesized that a Ca(2+)-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 endothelial cells and thus could represent an important mechanism in HCMV-induced cellular transendothelial migration and disruption of the endothelial integrity.
Scholz
M
M
Institut für Medizinische Virologie, Johann-Wolfgang-Goethe-Universität, Frankfurt am Main, Deutschland. m.scholz@em.uni-frankfurt.de
Blaheta
R A
RA
Vogel
J
J
Doerr
H W
HW
Cinatl
J
J
D002448:Cell Adhesion; D002450:Cell Communication / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000502:physiology* / Q000821:virology*; D006801:Humans; D007962:Leukocytes / Q000821:virology; D014407:Tumor Cells, Cultured
D016207:Cytokines