Oxidant inhibition of alphaLbeta2 integrin adhesion: evidence for coordinate effects on conformation and cytoskeleton linkage
| Autor: | Mark S. Curry, Bruce S. Edwards, James M. Gale, Martyn K. Robinson, Francisco Salazar, Jerry L. Born, Eileen A. Southon, Lloyd H. Graf |
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| Rok vydání: | 1998 |
| Předmět: |
Integrins
Immunology Integrin Epitope Dithiothreitol Arsenicals chemistry.chemical_compound Phosphoserine Adenosine Triphosphate Cell Adhesion Immunology and Allergy Humans Cytochalasin Phenylarsine oxide Sulfhydryl Compounds Cytoskeleton Cells Cultured biology Temperature Antibodies Monoclonal Cell Biology Adhesion Oxidants Lymphocyte Function-Associated Antigen-1 Cell biology Killer Cells Natural Phosphothreonine chemistry biology.protein Tetradecanoylphorbol Acetate Oxidation-Reduction Intracellular Signal Transduction |
| Zdroj: | Journal of leukocyte biology. 63(2) |
| ISSN: | 0741-5400 |
| Popis: | Dithiothreitol (DTT) and other dithiol antioxidants with closely spaced thiol pairs strongly activate leukocyte function antigen-1 (LFA-1, αLβ2 integrin) to bind intercellular adhesion molecule-1 (ICAM-1). Because direct biochemical modification of LFA-1 by DTT is not apparently involved, we investigated the possible role of a reduction-oxidation (redox)-sensitive adhesion-regulatory pathway. Phenylarsine oxide (PAO), an oxidant selectively reactive with closely spaced pairs of thiol groups, inhibited LFA-1-dependent adhesion of human natural killer and HSB2 T leukemia cells to murine cells expressing human ICAM-1. PAO also induced disappearance of a conformation-sensitive LFA-1 epitope recognized by KIM127 antibodies and promoted an increase in total apparent cytoskeleton-linked LFA-1 in which a novel cytochalasin D-resistant linkage was involved. Exposure of PAO-pretreated cells to DTT caused a decline in LFA-1/cytoskeleton linkages in conjunction with rapid restoration of KIM127 epitope expression and LFA-1 adhesive function. Implicating an intracellular site of action were findings that (1) an epitope-tagged PAO probe bound predominantly to intracellular proteins but not detectably to immunoprecipitation-purified LFA-1 chains, and (2) membrane permeant but not impermeant dithiol antioxidants reversed PAO adhesion-inhibitory effects. These results support the concept of a reversible redox-sensitive linkage between LFA-1 and cytoskeleton by which oxidants and antioxidants may exert profound opposing effects on LFA-1 conformation and adhesive function. |
| Databáze: | OpenAIRE |
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