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.

G PROTEIN COUPLED RECEPTORS MEDIATE FIBROBLAST CHEMOTAXIS INDUCED BY BRONCOALVEOLAR LAVAGE FLUID OF ARDS PATIENTS

FANELLI, VITO;PUNTORIERI, valeria;CAPPELLO, Paola;TERRAGNI, Pierpaolo;BOSCO, Maria Chiara;DEL SORBO, Lorenzo;MARTIN, ERICA LEANNE;MASCIA, Luciana;RANIERI, Vito Marco
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.
21 st Annual Congress ESICM
lisbon
21-24 september
34
49
49
http://icmjournal.esicm.org
V. Fanelli; V. Puntorieri; P. Cappello; P. Terragni; M. Bosco; L. Del Sorbo;E. L. Martin; L. Delsedime; L. Mascia; V. M. Ranieri
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/111967
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