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

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.