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ESAM supports neutrophil extravasation, activation of Rho, and VEGF-induced vascular permeability

Authors :
Ines Nasdala
Björn Petri
Andrej Khandoga
Alexander G. Khandoga
Dietmar Vestweber
Oliver Brandau
Frank Wegmann
Stefan Butz
Hang Li
Christian Moser
Fritz Krombach
Reinhard Fässler
Stefan Volkery
Source :
The Journal of Experimental Medicine
Publication Year :
2006

Abstract

Endothelial cell–selective adhesion molecule (ESAM) is specifically expressed at endothelial tight junctions and on platelets. To test whether ESAM is involved in leukocyte extravasation, we have generated mice carrying a disrupted ESAM gene and analyzed them in three different inflammation models. We found that recruitment of lymphocytes into inflamed skin was unaffected by the gene disruption. However, the migration of neutrophils into chemically inflamed peritoneum was inhibited by 70% at 2 h after stimulation, recovering at later time points. Analyzing neutrophil extravasation directly by intravital microscopy in the cremaster muscle revealed that leukocyte extravasation was reduced (50%) in ESAM−/− mice without affecting leukocyte rolling and adhesion. Depletion of >98% of circulating platelets did not abolish the ESAM deficiency–related inhibitory effect on neutrophil extravasation, indicating that it is only ESAM at endothelial tight junctions that is relevant for the extravasation process. Knocking down ESAM expression in endothelial cells resulted in reduced levels of activated Rho, a GTPase implicated in the destabilization of tight junctions. Indeed, vascular permeability stimulated by vascular endothelial growth factor was reduced in ESAM−/− mice. Collectively, ESAM at endothelial tight junctions participates in the migration of neutrophils through the vessel wall, possibly by influencing endothelial cell contacts.

Details

Language :
English
ISSN :
15409538 and 00221007
Volume :
203
Issue :
7
Database :
OpenAIRE
Journal :
The Journal of experimental medicine
Accession number :
edsair.doi.dedup.....d6b036782004fbb47b92e44ee33f9cb6