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Activation State of Α4β1 Integrin Controls Capture, Immobilization and Migration of Flowing Lymphocytes on Purified VCAM-1

  • Patricia Lalor
  • J. M. Clements
  • R. Pigott
  • M. J. Humphries
  • J. H. Spragg
  • G. B. Nash
Part of the NATO ASI Series book series (NSSA, volume 294)

Abstract

Vascular cell adhesion molecule-1 (VCAM-1) is expressed on endothelial cells following cytokine stimulation, and can bind leukocyte α4β1 integrin. Adhesion of flowing human lymphocytes to VCAM-1 was analyzed through use of purified recombinant VCAM-1 immobilized onto plastic in a flow chamber. Integrin-mediated attachment supported adhesion of lymphocytes at physiological shear rates, but the nature of attachment was dependent on the concentration of VCAM-1 (10–100 μg/ml). At low concentration most adherent cells were rolling (~75%) but this decreased to <5% at 100 μg/ml VCAM-1. Activation of α4β1 integrin by Mn++ or monoclonal antibodies 12G10 and TS2/16 induced significant increases in lymphocyte adhesion only at low VCAM-1 concentration, and converted rolling adhesion to the stationary form. Treatment with phorbol ester had a similar effect, but also induced adherent lymphocytes to flatten and spread over the VCAM-1. These results suggest that the adhesive behavior of lymphocytes on VCAM-1, i.e. rolling adhesion vs. stationary adhesion and spreading, is dependent on the activation state of VLA-4, and that ligation of high concentrations of VCAM-1 is sufficient to induce activation of this integrin. Pretreatment of lymphocytes with the metabolic inhibitor sodium azide, or chelation of intracelluar Ca++ caused lymphocytes to remain rolling on 100 µg/ml VCAM-1, supporting the concept of ligand-induced, energy-dependent signaling. This implies that regulation of VCAM-1 concentration and integrin activation in vivo could control the nature of lymphocyte adhesion, with a co-expressed stimulus probably required for subsequent migration.

Keywords

Phorbol Ester Vascular Cell Adhesion Flow Chamber Adhesive Behavior Cytokine Stimulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Patricia Lalor
    • 1
  • J. M. Clements
    • 2
  • R. Pigott
    • 2
  • M. J. Humphries
    • 3
  • J. H. Spragg
    • 4
  • G. B. Nash
    • 1
  1. 1.Department of PhysiologyThe Medical SchoolBirminghamUK
  2. 2.Neures Ltd.Abingdon, OxfordshireUK
  3. 3.Biological SciencesManchester UniversityManchesterUK
  4. 4.Yamanouchi Research InstituteOxfordUK

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