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PMID: 9456328 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

LFA-1-mediated adhesion is regulated by cytoskeletal restraint and by a Ca2+-dependent protease, calpain.

The Journal of cell biology ·Vol. 140 ·No. 3 ·1998-02-09 ·Pages 699-707

Stewart MP, McDowall A, Hogg N

Abstract

The activity of integrins on leukocytes is kept under tight control to avoid inappropriate adhesion while these cells are circulating in blood or migrating through tissues. Using lymphocyte function-associated antigen-1 (LFA-1) on T cells as a model, we have investigated adhesion to ligand intercellular adhesion molecule-1 induced by the Ca2+ mobilizers, ionomycin, 2, 5-di-t-butylhydroquinone, and thapsigargin, and the well studied stimulators such as phorbol ester and cross-linking of the antigen-specific T cell receptor (TCR)-CD3 complex. We report here that after exposure of T cells to these agonists, integrin is released from cytoskeletal control by the Ca2+-induced activation of a calpain-like enzyme, and adhesive contact between cells is strengthened by means of the clustering of mobilized LFA-1 on the membrane. We propose that methods of leukocyte stimulation that cause Ca2+ fluxes induce LFA-1 adhesion by regulation of calpain activity. These findings suggest a mechanism whereby engagement of the TCR could promote adhesion strengthening at an early stage of interaction with an antigen-presenting cell.

MeSH Terms
Calcium/metabolism Calpain/metabolism Cell Adhesion Cells, Cultured Cytoskeleton/physiology Depsipeptides Humans Hydroquinones/pharmacology Intercellular Adhesion Molecule-1/metabolism Ionomycin/pharmacology Lymphocyte Function-Associated Antigen-1/analysis,physiology Microscopy, Confocal Peptides, Cyclic/pharmacology Signal Transduction T-Lymphocytes/cytology,physiology Thapsigargin/pharmacology
Chemicals
Depsipeptides Hydroquinones Lymphocyte Function-Associated Antigen-1 Peptides, Cyclic jasplakinolide Intercellular Adhesion Molecule-1 2,5-di-tert-butylhydroquinone Ionomycin Thapsigargin Calpain Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Stewart M P
Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
McDowall A
Hogg N
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.140.3.699
Published
1998-02-09
Pages
699-707
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2140165
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.140.3.699 PMC Full Text View journal details
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