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EnglishINTRODUCTION. Alveolar fibrosis in the late phase of ARDS derives from an abnormal wound healing process. Fibroblast chemotaxis is a critical step in lung repair and fibrosis. Several chemoattractants are present in the broncoalveolar lavage (BAL) fluid of ARDS patients. Chemotaxis is mainly mediated by G-protein coupled receptors, which trigger in turn multiple intracellular signalling pathways. Our hypothesis is that BAL fluid of ARDS patients induces fibroblast chemotaxis and can be inhibited by blockade of G-protein coupled receptors. METHODS. A chemotaxis assay was performed using lung fibroblasts (NIH-3T3) stimulated with BAL from patients with early or without ARDS. To chemically inhibit G-protein coupled receptors, fibroblasts were pre-treated with pertussis toxin (PTX). The number of migrated cells in response to BAL stimulation was counted. Stimulation of fibroblast with medium or stromal cell-derived factor (SDF)-1 were used as negative and positive controls respectively. CONCLUSION. G-protein coupled receptors are involved in fibroblast migration induced by alveolar fluid milieu of patients with ARDS. Therefore, the development of specific drugs designed to inhibit G-protein coupled receptors may represent a potential therapeutic treatment to prevent formation of alveolar fibrosis in ARDS.
| Titolo: | G PROTEIN COUPLED RECEPTORS MEDIATE FIBROBLAST CHEMOTAXIS INDUCED BY BRONCOALVEOLAR LAVAGE FLUID OF ARDS PATIENTS |
| Autori Riconosciuti: | |
| Autori: | V. Fanelli; V. Puntorieri; P. Cappello; P. Terragni; M. Bosco; L. Del Sorbo;E. L. Martin; L. Delsedime; L. Mascia; V. M. Ranieri |
| Data di pubblicazione: | 2008 |
| Abstract: | INTRODUCTION. Alveolar fibrosis in the late phase of ARDS derives from an abnormal wound healing process. Fibroblast chemotaxis is a critical step in lung repair and fibrosis. Several chemoattractants are present in the broncoalveolar lavage (BAL) fluid of ARDS patients. Chemotaxis is mainly mediated by G-protein coupled receptors, which trigger in turn multiple intracellular signalling pathways. Our hypothesis is that BAL fluid of ARDS patients induces fibroblast chemotaxis and can be inhibited by blockade of G-protein coupled receptors. METHODS. A chemotaxis assay was performed using lung fibroblasts (NIH-3T3) stimulated with BAL from patients with early or without ARDS. To chemically inhibit G-protein coupled receptors, fibroblasts were pre-treated with pertussis toxin (PTX). The number of migrated cells in response to BAL stimulation was counted. Stimulation of fibroblast with medium or stromal cell-derived factor (SDF)-1 were used as negative and positive controls respectively. CONCLUSION. G-protein coupled receptors are involved in fibroblast migration induced by alveolar fluid milieu of patients with ARDS. Therefore, the development of specific drugs designed to inhibit G-protein coupled receptors may represent a potential therapeutic treatment to prevent formation of alveolar fibrosis in ARDS. |
| Volume: | 34 |
| Pagina iniziale: | 49 |
| Pagina finale: | 49 |
| Nome del convegno: | 21 st Annual Congress ESICM |
| Luogo del convegno: | lisbon |
| Anno del convegno: | 21-24 september |
| URL: | http://icmjournal.esicm.org |
| Rivista: | INTENSIVE CARE MEDICINE |
| Appare nelle tipologie: | 04B-Conference paper in rivista |
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