LFA-1-mediated Adhesion Is Regulated by Cytoskeletal Restraint and by a Ca2+-dependent Protease, Calpain

doi:10.1083/jcb.140.3.699

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© The Rockefeller University Press, 0021-9525/1998//699 $5.00
The Journal of Cell Biology, Volume 140, Number 3, , 1998 699-707

Article

LFA-1–mediated Adhesion Is Regulated by Cytoskeletal Restraint and by a Ca²⁺-dependent Protease, Calpain

Mairi P. Stewart, Alison McDowall, and Nancy Hogg

Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom

The activity of integrins on leukocytes is kept under tightcontrol to avoid inappropriate adhesion while these cells arecirculating in blood or migrating through tissues. Using lymphocytefunction-associated antigen-1 (LFA-1) on T cells as a model,we have investigated adhesion to ligand intercellular adhesionmolecule-1 induced by the Ca²⁺ mobilizers, ionomycin, 2,5-di-t-butylhydroquinone,and thapsigargin, and the well studied stimulators such asphorbol ester and cross-linking of the antigen-specific T cellreceptor (TCR)– CD3 complex. We report here that afterexposure of T cells to these agonists, integrin is releasedfrom cytoskeletal control by the Ca²⁺-induced activation ofa calpain-like enzyme, and adhesive contact between cellsis strengthened by means of the clustering of mobilized LFA-1on the membrane. We propose that methods of leukocyte stimulationthat cause Ca²⁺ fluxes induce LFA-1 adhesion by regulationof calpain activity. These findings suggest a mechanism whereby engagement of the TCR could promote adhesion strengtheningat an early stage of interaction with an antigen-presentingcell.

Abbreviations used in this paper: dBHQ, 2,5-di-t-butylhydroquinone; ICAM-1, intercellular adhesion molecule-1; LFA-1, lymphocyte function-associate antigen-1; MLCK, myosin light chain kinase; Pdbu, phorbol 12,13 dibutyrate; PKC, protein kinase C; sICAM-1, soluble intercellular adhesion molecule-1; TCR, T cell receptor.

Address all correspondence to Nancy Hogg, Leukocyte AdhesionLaboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields,London WC2A 3PX, United Kingdom. Tel.: 44 171 269 3255. Fax:44 171 269 3093. E-mail: hogg{at}icrf.icnet.uk

M.P. Stewart and A. McDowall contributed equally to this work.

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