A down-regulatable E-selectin ligand is functionally important for PSGL-1–independent leukocyte–endothelial cell interactions
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- Renata C. O. Zanardo
- From the Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; and Institut für Zellbiologie, Zentrum für Molekularbiologie der Entzündung (ZMBE), Universität Münster and Max-Planck-Institute, Münster, Germany.
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- Claudine S. Bonder
- From the Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; and Institut für Zellbiologie, Zentrum für Molekularbiologie der Entzündung (ZMBE), Universität Münster and Max-Planck-Institute, Münster, Germany.
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- John M. Hwang
- From the Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; and Institut für Zellbiologie, Zentrum für Molekularbiologie der Entzündung (ZMBE), Universität Münster and Max-Planck-Institute, Münster, Germany.
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- Graciela Andonegui
- From the Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; and Institut für Zellbiologie, Zentrum für Molekularbiologie der Entzündung (ZMBE), Universität Münster and Max-Planck-Institute, Münster, Germany.
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- Lixin Liu
- From the Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; and Institut für Zellbiologie, Zentrum für Molekularbiologie der Entzündung (ZMBE), Universität Münster and Max-Planck-Institute, Münster, Germany.
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- Dietmar Vestweber
- From the Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; and Institut für Zellbiologie, Zentrum für Molekularbiologie der Entzündung (ZMBE), Universität Münster and Max-Planck-Institute, Münster, Germany.
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- Lori Zbytnuik
- From the Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; and Institut für Zellbiologie, Zentrum für Molekularbiologie der Entzündung (ZMBE), Universität Münster and Max-Planck-Institute, Münster, Germany.
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- Paul Kubes
- From the Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; and Institut für Zellbiologie, Zentrum für Molekularbiologie der Entzündung (ZMBE), Universität Münster and Max-Planck-Institute, Münster, Germany.
Description
<jats:p>P-selectin glycoprotein-1 (PSGL-1) supports P-selectin–dependent rolling in vivo and in vitro. However, controversy exists regarding the importance of PSGL-1–dependent and –independent E-selectin rolling. Using antibodies against PSGL-1 and PSGL-1-/- mice, we demonstrated abolition of P-selectin–dependent rolling but only partial inhibition of E-selectin–mediated rolling in the cremaster microcirculation following local administration of tumor necrosis factor α (TNF-α). In vitro studies demonstrated that binding of recombinant mouse E-selectin chimera to PSGL-1-/- neutrophils was dramatically decreased in mice treated systemically but not locally with TNF-α. Further, PSGL-1 blockade abolished E-selectin–dependent rolling in wild-type mice following systemic TNF-α administration but not local TNF-α administration. Together, these data support an E-selectin ligand present on PSGL-1-/- neutrophils that is down-regulatable upon systemic but not local activation. To determine whether the PSGL-1–independent E-selectin ligand was physiologically important, we used a P- and E-selectin–dependent cutaneous contact hypersensitivity model. Binding studies showed no E-selectin ligand down-regulation in this model. The few cells that rolled on E-selectin ligand following PSGL-1 antibody administration or in PSGL-1 deficiency were sufficient to induce profound contact hypersensitivity. In conclusion, E-selectin mediates PSGL-1–dependent and independent rolling and the latter can be down-regulated by systemic activation and can replace PSGL-1 to support the development of inflammation.</jats:p>
Journal
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- Blood
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Blood 104 (12), 3766-3773, 2004-12-01
American Society of Hematology
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Keywords
Details 詳細情報について
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- CRID
- 1362262945661224064
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- ISSN
- 15280020
- 00064971
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- Data Source
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- Crossref