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.
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10 July 2006
Brief Definitive Report|
July 03 2006
ESAM supports neutrophil extravasation, activation of Rho, and VEGF-induced vascular permeability
Frank Wegmann,
Frank Wegmann
1Max-Planck-Institute for Molecular Biomedicine and Institute of Cell Biology, University of Münster, D-48149 Münster, Germany
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Björn Petri,
Björn Petri
1Max-Planck-Institute for Molecular Biomedicine and Institute of Cell Biology, University of Münster, D-48149 Münster, Germany
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Alexander Georg Khandoga,
Alexander Georg Khandoga
2Institute for Surgical Research, University of Munich, D-81377 Munich, Germany
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Christian Moser,
Christian Moser
2Institute for Surgical Research, University of Munich, D-81377 Munich, Germany
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Andrej Khandoga,
Andrej Khandoga
2Institute for Surgical Research, University of Munich, D-81377 Munich, Germany
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Stefan Volkery,
Stefan Volkery
1Max-Planck-Institute for Molecular Biomedicine and Institute of Cell Biology, University of Münster, D-48149 Münster, Germany
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Hang Li,
Hang Li
1Max-Planck-Institute for Molecular Biomedicine and Institute of Cell Biology, University of Münster, D-48149 Münster, Germany
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Ines Nasdala,
Ines Nasdala
1Max-Planck-Institute for Molecular Biomedicine and Institute of Cell Biology, University of Münster, D-48149 Münster, Germany
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Oliver Brandau,
Oliver Brandau
3Max-Planck-Institute for Biochemistry, D-82152 Martinsried, Germany
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Reinhard Fässler,
Reinhard Fässler
3Max-Planck-Institute for Biochemistry, D-82152 Martinsried, Germany
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Stefan Butz,
Stefan Butz
1Max-Planck-Institute for Molecular Biomedicine and Institute of Cell Biology, University of Münster, D-48149 Münster, Germany
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Fritz Krombach,
Fritz Krombach
2Institute for Surgical Research, University of Munich, D-81377 Munich, Germany
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Dietmar Vestweber
Dietmar Vestweber
1Max-Planck-Institute for Molecular Biomedicine and Institute of Cell Biology, University of Münster, D-48149 Münster, Germany
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Frank Wegmann
1Max-Planck-Institute for Molecular Biomedicine and Institute of Cell Biology, University of Münster, D-48149 Münster, Germany
Björn Petri
1Max-Planck-Institute for Molecular Biomedicine and Institute of Cell Biology, University of Münster, D-48149 Münster, Germany
Alexander Georg Khandoga
2Institute for Surgical Research, University of Munich, D-81377 Munich, Germany
Christian Moser
2Institute for Surgical Research, University of Munich, D-81377 Munich, Germany
Andrej Khandoga
2Institute for Surgical Research, University of Munich, D-81377 Munich, Germany
Stefan Volkery
1Max-Planck-Institute for Molecular Biomedicine and Institute of Cell Biology, University of Münster, D-48149 Münster, Germany
Hang Li
1Max-Planck-Institute for Molecular Biomedicine and Institute of Cell Biology, University of Münster, D-48149 Münster, Germany
Ines Nasdala
1Max-Planck-Institute for Molecular Biomedicine and Institute of Cell Biology, University of Münster, D-48149 Münster, Germany
Oliver Brandau
3Max-Planck-Institute for Biochemistry, D-82152 Martinsried, Germany
Reinhard Fässler
3Max-Planck-Institute for Biochemistry, D-82152 Martinsried, Germany
Stefan Butz
1Max-Planck-Institute for Molecular Biomedicine and Institute of Cell Biology, University of Münster, D-48149 Münster, Germany
Fritz Krombach
2Institute for Surgical Research, University of Munich, D-81377 Munich, Germany
Dietmar Vestweber
1Max-Planck-Institute for Molecular Biomedicine and Institute of Cell Biology, University of Münster, D-48149 Münster, Germany
CORRESPONDENCE Dietmar Vestweber: [email protected] OR Stefan Butz: [email protected]
F. Wegmann and B. Petri contributed equally to this work.
Received:
April 05 2006
Accepted:
June 02 2006
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2006
J Exp Med (2006) 203 (7): 1671–1677.
Article history
Received:
April 05 2006
Accepted:
June 02 2006
Citation
Frank Wegmann, Björn Petri, Alexander Georg Khandoga, Christian Moser, Andrej Khandoga, Stefan Volkery, Hang Li, Ines Nasdala, Oliver Brandau, Reinhard Fässler, Stefan Butz, Fritz Krombach, Dietmar Vestweber; ESAM supports neutrophil extravasation, activation of Rho, and VEGF-induced vascular permeability . J Exp Med 10 July 2006; 203 (7): 1671–1677. doi: https://doi.org/10.1084/jem.20060565
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