Feedback modulation of ligand-engaged αL/β2 leukocyte integrin (LFA-1) by cyclic AMP-dependent protein kinase

Patrizia Rovere, Luca A Inverardi, Jeffrey R. Bender, Ruggero Pardi

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Rapid interconversion between a firmly adherent and a nonadherent, circulating phenotype is a distinctive feature of mature leukocytes and is thought to be essential for efficient immune surveillance. Leukocyte adhesion is a finely regulated process controlled in part by reversible, activation- dependent up-regulation of β1- and β2-integrin function. To investigate the molecular basis of such reversibility in human T lymphocytes, we developed a model of αL/β2 (LFA-1)-dependent adhesion that uses a heterologous cell line expressing human intercellular adhesion molecule-1 as a selected ligand. We show here that intracellular cAMP elevation, followed by cAMP-dependent kinase activation, promotes T cell deadhesion by disassembling the actin-based cytoskeleton, thus dissociating LFA-1 from cytoskeletal anchoring proteins that normally connect the adhesion receptor to F-actin in lymphocytes engaged in intercellular adhesion. Cells costimulated via the CD3 and LFA-1 receptors by specific Abs or by binding to intercellular adhesion molecule-1 display gradual and persistent intracellular cAMP elevations due to the synergistic induction of a protein kinase C-dependent adenylyl cyclase isoform. On the basis of these findings, we propose a feedback model for short term regulation of leukocyte integrins, involving sequential, integrin-dependent activation of the protein kinase C and adenylyl cyclase/cAMP-dependent kinase enzymatic pathways and leading to disengagement of the adhesion receptor from its specific ligand.

Original languageEnglish
Pages (from-to)2273-2279
Number of pages7
JournalJournal of Immunology
Volume156
Issue number6
StatePublished - Mar 15 1996
Externally publishedYes

Fingerprint

Lymphocyte Function-Associated Antigen-1
Cyclic AMP-Dependent Protein Kinases
Integrins
Leukocytes
Intercellular Adhesion Molecule-1
Ligands
Adenylyl Cyclases
Protein Kinase C
Phosphotransferases
T-Lymphocytes
Cytoskeletal Proteins
Actin Cytoskeleton
Actins
Protein Isoforms
Up-Regulation
Lymphocytes
Phenotype
Cell Line
adhesion receptor

ASJC Scopus subject areas

  • Immunology

Cite this

Rovere, P., Inverardi, L. A., Bender, J. R., & Pardi, R. (1996). Feedback modulation of ligand-engaged αL/β2 leukocyte integrin (LFA-1) by cyclic AMP-dependent protein kinase. Journal of Immunology, 156(6), 2273-2279.

Feedback modulation of ligand-engaged αL/β2 leukocyte integrin (LFA-1) by cyclic AMP-dependent protein kinase. / Rovere, Patrizia; Inverardi, Luca A; Bender, Jeffrey R.; Pardi, Ruggero.

In: Journal of Immunology, Vol. 156, No. 6, 15.03.1996, p. 2273-2279.

Research output: Contribution to journalArticle

Rovere, P, Inverardi, LA, Bender, JR & Pardi, R 1996, 'Feedback modulation of ligand-engaged αL/β2 leukocyte integrin (LFA-1) by cyclic AMP-dependent protein kinase', Journal of Immunology, vol. 156, no. 6, pp. 2273-2279.
Rovere, Patrizia ; Inverardi, Luca A ; Bender, Jeffrey R. ; Pardi, Ruggero. / Feedback modulation of ligand-engaged αL/β2 leukocyte integrin (LFA-1) by cyclic AMP-dependent protein kinase. In: Journal of Immunology. 1996 ; Vol. 156, No. 6. pp. 2273-2279.
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