Leukocyte recruitment into inflammatory sites is initiated by a reversible transient adhesive contact with the endothelium called leukocyte rolling, which is thought to be mediated by the selectin family of adhesion molecules. Selectin-mediated rolling precedes inflammatory cell emigration, which is significantly impaired in both P- and L-selectin gene-deficient mice. We report here that approximately 13% of all leukocytes passing venules of the cremaster muscle of wild-type mice roll along the endothelium at < 20 min after surgical dissection. Rolling leukocyte flux fraction reaches a maximum of 28% at 40-60 min and returns to 13% at 80-120 min. In P-selectin-deficient mice, rolling is absent initially and reaches 5% at 80-120 min. Rolling flux fraction in L-selectin-deficient mice is similar to wild type initially and declines to 5% at 80-120 min. In both wild-type and L-selectin-deficient mice, initial leukocyte rolling (0-60 min) is completely blocked by the P-selectin monoclonal antibody (mAb) RB40.34, but unaffected by L-selectin mAb MEL-14. Conversely, rolling at later time points (60-120 min) is inhibited by mAb MEL-14 but not by mAb RB40.34. After treatment with tumor necrosis factor (TNF)-alpha for 2 h, approximately 24% of all passing leukocytes roll in cremaster venules of wild-type and P-selectin gene-deficient mice. Rolling in TNF-alpha-treated mice is unaffected by P-selectin mAb or E-selectin mAb 10E9.6. By contrast, rolling in TNF-alpha-treated P-selectin-deficient mice is completely blocked by L-selectin mAb. These data show that P-selectin is important during the initial induction of leukocyte rolling after tissue trauma. At later time points and in TNF-alpha-treated preparations, rolling is largely L-selectin dependent. Under the conditions tested, we are unable to find evidence for involvement of E-selectin in leukocyte rolling in mice.
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February 01 1995
Sequential contribution of L- and P-selectin to leukocyte rolling in vivo.
K Ley,
K Ley
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville 22908.
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D C Bullard,
D C Bullard
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville 22908.
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M L Arbonés,
M L Arbonés
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville 22908.
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R Bosse,
R Bosse
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville 22908.
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D Vestweber,
D Vestweber
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville 22908.
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T F Tedder,
T F Tedder
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville 22908.
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A L Beaudet
A L Beaudet
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville 22908.
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K Ley
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville 22908.
D C Bullard
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville 22908.
M L Arbonés
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville 22908.
R Bosse
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville 22908.
D Vestweber
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville 22908.
T F Tedder
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville 22908.
A L Beaudet
Department of Biomedical Engineering, University of Virginia Medical School, Charlottesville 22908.
Online Issn: 1540-9538
Print Issn: 0022-1007
J Exp Med (1995) 181 (2): 669–675.
Citation
K Ley, D C Bullard, M L Arbonés, R Bosse, D Vestweber, T F Tedder, A L Beaudet; Sequential contribution of L- and P-selectin to leukocyte rolling in vivo.. J Exp Med 1 February 1995; 181 (2): 669–675. doi: https://doi.org/10.1084/jem.181.2.669
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