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.
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 |