Role of intracellular chloride in the reversible activation of neutrophil ß2 integrins: A lesson from TNF stimulation
Autor: | Rita Cramer, Pierluigi Patriarca, Renzo Menegazzi, Pietro Dri, Sara Busetto |
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Přispěvatelé: | Menegazzi, Renzo, Busetto, S, Cramer, R, Dri, Pietro, Patriarca, Pierluigi |
Rok vydání: | 2000 |
Předmět: |
Agonist
Intracellular Fluid medicine.drug_class Neutrophils Protein Conformation Immunology Stimulation Buffers Epitope Antiporters Neutrophil Activation β2 integrin Basal (phylogenetics) Epitopes Chlorides medicine Cell Adhesion Immunology and Allergy Humans Chemistry Tumor Necrosis Factor-alpha Butylated Hydroxytoluene Hydrogen-Ion Concentration Cell biology Biochemistry Cytoplasm CD18 Antigens Tumor necrosis factor alpha Intracellular |
Zdroj: | Scopus-Elsevier |
Popis: | The process of beta(2) integrin activation, which enhances the interaction of these heterodimers with ligands, plays a crucial role in the adherence-dependent neutrophilic polymorphonuclear leukocytes' (PMN) responses to TNF. Our previous observation, showing that a marked decrease of the high basal Cl(-) content (Cl(-)(i)) is an essential step in the TNF-induced activation of PMN, stimulated this study, which investigates the role of alterations of Cl(-)(i) in the activation of beta(2) integrins triggered by TNF. Here we show that TNF enhances the expression of activation-specific neoepitopes of beta(2) integrins, namely, epitope 24, a unique epitope present on all three leukocyte integrin alpha subunits, and epitope CBRM1/5, localized to the I domain on the alpha-chain of Mac-1 (CD11bCD18). Moreover, we demonstrate that the conformational changes underlying the expression of the neoepitopes are dependent on a drop in Cl(-)(i) because 1) inhibition of Cl(-)(i) decrease is invariably accompanied by inhibition of beta(2) integrin activation, 2) Cl(-)(i) decrease induced by means other than agonist stimulation, i.e., by placing PMN in Cl(-)-free buffers, activates beta(2) integrins, and 3) restoration of the original Cl(-)(i) levels is accompanied by deactivation of beta(2) integrins. We also show that Cl(-)(i) decrease is required for TNF-induced cytoplasmic alkalinization, but such a rise in pH(i) does not seem to be relevant for beta(2) integrin activation. The results of our study emphasize the role of Cl(-) as a new PMN "second messenger." |
Databáze: | OpenAIRE |
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