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ESAM supports neutrophil extravasation, activation of Rho, and VEGF-induced vascular permeability
- 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.
- Subjects :
- Male
Vascular Endothelial Growth Factor A
rho GTP-Binding Proteins
Neutrophils
Immunology
Vascular permeability
Leukocyte Rolling
Cell Communication
Biology
Capillary Permeability
Mice
Cell Movement
Animals
Immunology and Allergy
Mice, Knockout
Neutrophil extravasation
Tight junction
Brief Definitive Report
Cell Biology
Leukocyte extravasation
Extravasation
Cell biology
Enzyme Activation
Endothelial stem cell
Vascular endothelial growth factor A
Brief Definitive Reports
Female
Cell Adhesion Molecules
Subjects
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