Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 316K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Levite, M. Articles by Lider, O. Search for Related Content PubMed PubMed Citation Articles by Levite, M. Articles by Lider, O. Social Bookmarking                            What's this?

Original Article

Mia Levite^a, Liora Cahalon^a, Asher Peretz^b, Rami Hershkoviz^a, Alex Sobko^b, Amiram Ariel^a, Rooma Desai^b, Bernard Attali^b, and Ofer Lider^a

^a Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
^b Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.972-8-9344173972-8-9343556

mia.levite{at}weizmann.ac.il

Elevated extracellular K⁺ ([K⁺]_o), in the absence of "classical" immunological stimulatory signals, was found to itself be a sufficient stimulus to activate T cell β1 integrin moieties, and to induce integrin-mediated adhesion and migration. Gating of T cell voltage-gated K⁺ channels (Kv1.3) appears to be the crucial "decision-making" step, through which various physiological factors, including elevated [K⁺]_o levels, affect the T cell β1 integrin function: opening of the channel leads to function, whereas its blockage prevents it. In support of this notion, we found that the proadhesive effects of the chemokine macrophage-inflammatory protein 1β, the neuropeptide calcitonin gene–related peptide (CGRP), as well as elevated [K⁺]_o levels, are blocked by specific Kv1.3 channel blockers, and that the unique physiological ability of substance P to inhibit T cell adhesion correlates with Kv1.3 inhibition. Interestingly, the Kv1.3 channels and the β1 integrins coimmunoprecipitate, suggesting that their physical association underlies their functional cooperation on the T cell surface. This study shows that T cells can be activated and driven to integrin function by a pathway that does not involve any of its specific receptors (i.e., by elevated [K⁺]_o). In addition, our results suggest that undesired T cell integrin function in a series of pathological conditions can be arrested by molecules that block the Kv1.3 channels.

Key Words: T cells • extracellular K⁺ • potassium channels • integrins • neuroimmunomodulation

Abbreviations used in this paper: 4AP, 4-aminopyridine; CGRP, calcitonin gene–related peptide; ChTX, charybdotoxin; CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione; DiBAC₄(3), bis-(1,3-dibutylbarbituric acid) trimethine oxonol; ECM, extracellular matrix; FN, fibronectin; [K⁺]_o, extracellular K⁺; KaTx, kaliotoxin; MgTx, margatoxin; MIP, macrophage-inflammatory protein; NoTx, noxioustoxin; Sub P, substance P; TEA, tetraethylammonium; TTX, tetrodotoxin; VLA, very late antigen.

© 2000 The Rockefeller University Press

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS