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Alpha 4 beta 1 integrin/VCAM-1 interaction activates alpha L beta 2 integrin-mediated adhesion to ICAM-1 in human T cells.
J Immunol. 2000 Jan 15; 164(2):746-53.JI

Abstract

Modulation of integrin affinity and/or avidity provides a regulatory mechanism by which leukocyte adhesion to endothelium is strengthened or weakened at different stages of emigration. In this study, we demonstrate that binding of high-affinity alpha 4 beta 1 integrins to VCAM-1 strengthens alpha L beta 2 integrin-mediated adhesion. The strength of adhesion of Jurkat cells, a human leukemia T cell line, or MnCl2-treated peripheral blood T cells to immobilized chimeric human VCAM-1/Fc, ICAM-1/Fc, or both was quantified using parallel plate flow chamber leukocyte detachment assays in which shear stress was increased incrementally (0.5-30 dynes/cm2). The strength of adhesion to VCAM-1 plus ICAM-1, or to a 40-kDa fragment of fibronectin containing the CS-1 exon plus ICAM-1, was greater than the sum of adhesion to each molecule alone. Treatment of Jurkat or blood T cells with soluble cross-linked VCAM-1/Fc or HP2/1, a mAb to alpha 4, significantly increased adhesion to ICAM-1. These treatments induced clustering of alpha L beta 2 integrins, but not the high-affinity beta 2 integrin epitope recognized by mAb 24. Up-regulated adhesion to ICAM-1 was abolished by cytochalasin D, an inhibitor of cytoskeletal rearrangement. Taken together, our data suggest that the binding of VCAM-1 or fibronectin to alpha 4 beta 1 integrins initiates a signaling pathway that increases beta 2 integrin avidity but not affinity. A role for the cytoskeleton is implicated in this process.

Authors+Show Affiliations

Department of Laboratory Medicine, University of Toronto, Toronto General Hospital Research Institute, Toronto, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10623819

Citation

Chan, J R., et al. "Alpha 4 Beta 1 integrin/VCAM-1 Interaction Activates Alpha L Beta 2 Integrin-mediated Adhesion to ICAM-1 in Human T Cells." Journal of Immunology (Baltimore, Md. : 1950), vol. 164, no. 2, 2000, pp. 746-53.
Chan JR, Hyduk SJ, Cybulsky MI. Alpha 4 beta 1 integrin/VCAM-1 interaction activates alpha L beta 2 integrin-mediated adhesion to ICAM-1 in human T cells. J Immunol. 2000;164(2):746-53.
Chan, J. R., Hyduk, S. J., & Cybulsky, M. I. (2000). Alpha 4 beta 1 integrin/VCAM-1 interaction activates alpha L beta 2 integrin-mediated adhesion to ICAM-1 in human T cells. Journal of Immunology (Baltimore, Md. : 1950), 164(2), 746-53.
Chan JR, Hyduk SJ, Cybulsky MI. Alpha 4 Beta 1 integrin/VCAM-1 Interaction Activates Alpha L Beta 2 Integrin-mediated Adhesion to ICAM-1 in Human T Cells. J Immunol. 2000 Jan 15;164(2):746-53. PubMed PMID: 10623819.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alpha 4 beta 1 integrin/VCAM-1 interaction activates alpha L beta 2 integrin-mediated adhesion to ICAM-1 in human T cells. AU - Chan,J R, AU - Hyduk,S J, AU - Cybulsky,M I, PY - 2000/1/7/pubmed PY - 2000/1/7/medline PY - 2000/1/7/entrez SP - 746 EP - 53 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 164 IS - 2 N2 - Modulation of integrin affinity and/or avidity provides a regulatory mechanism by which leukocyte adhesion to endothelium is strengthened or weakened at different stages of emigration. In this study, we demonstrate that binding of high-affinity alpha 4 beta 1 integrins to VCAM-1 strengthens alpha L beta 2 integrin-mediated adhesion. The strength of adhesion of Jurkat cells, a human leukemia T cell line, or MnCl2-treated peripheral blood T cells to immobilized chimeric human VCAM-1/Fc, ICAM-1/Fc, or both was quantified using parallel plate flow chamber leukocyte detachment assays in which shear stress was increased incrementally (0.5-30 dynes/cm2). The strength of adhesion to VCAM-1 plus ICAM-1, or to a 40-kDa fragment of fibronectin containing the CS-1 exon plus ICAM-1, was greater than the sum of adhesion to each molecule alone. Treatment of Jurkat or blood T cells with soluble cross-linked VCAM-1/Fc or HP2/1, a mAb to alpha 4, significantly increased adhesion to ICAM-1. These treatments induced clustering of alpha L beta 2 integrins, but not the high-affinity beta 2 integrin epitope recognized by mAb 24. Up-regulated adhesion to ICAM-1 was abolished by cytochalasin D, an inhibitor of cytoskeletal rearrangement. Taken together, our data suggest that the binding of VCAM-1 or fibronectin to alpha 4 beta 1 integrins initiates a signaling pathway that increases beta 2 integrin avidity but not affinity. A role for the cytoskeleton is implicated in this process. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10623819/Alpha_4_beta_1_integrin/VCAM_1_interaction_activates_alpha_L_beta_2_integrin_mediated_adhesion_to_ICAM_1_in_human_T_cells_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10623819 DB - PRIME DP - Unbound Medicine ER -