Delay of airway epithelial wound repair in COPD is associated with airflow obstruction severity.
Fiche publication
Date publication
novembre 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Dr PREVOST Alain
Tous les auteurs :
Perotin JM, Adam D, Vella-Boucaud J, Delepine G, Sandu S, Jonvel AC, Prevost A, Berthiot G, Pison C, Lebargy F, Birembaut P, Coraux C, Deslee G
Lien Pubmed
Résumé
BackgroundAirway epithelium integrity is essential to maintain its role of mechanical and functional barrier. Recurrent epithelial injuries require a complex mechanism of repair to restore its integrity. In chronic obstructive pulmonary disease (COPD), an abnormal airway epithelial repair may participate in airway remodeling. The objective was to determine if airway epithelial wound repair of airway epithelium is abnormal in COPD.MethodsPatients scheduled for lung resection were prospectively recruited. Demographic, clinical data and pulmonary function tests results were recorded. Emphysema was visually scored and histological remodeling features were noted. Primary bronchial epithelial cells (BEC) were extracted and cultured for wound closure assay. We determined the mean speed of wound closure (MSWC) and cell proliferation index, matrix metalloprotease (MMP)-2, MMP-9 and cytokines levels in supernatants of BEC 18 hours after cell wounding. In a subset of patients, bronchiolar epithelial cells were also cultured for wound closure assay for MSWC analyze.Results13 COPD and 7 non COPD patients were included. The severity of airflow obstruction and the severity of emphysema were associated with a lower MSWC in BEC (p inverted question mark= inverted question mark0.01, 95%CI [0.15-0.80]; p inverted question mark= inverted question mark0.04, 95%CI [ inverted question mark0.77;-0.03] respectively). Cell proliferation index was decreased in COPD patients (19 inverted question mark+/- inverted question mark6% in COPD vs 27 inverted question mark+/- inverted question mark3% in non COPD, p inverted question mark= inverted question mark0.04). The severity of COPD was associated with a lower level of MMP-2 (7.8 inverted question mark+/- inverted question mark2 105 AU in COPD GOLD D vs 12.8 inverted question mark+/- inverted question mark0.13 105 AU in COPD GOLD A, p inverted question mark= inverted question mark0.04) and a lower level of IL-4 (p inverted question mark= inverted question mark0.03, 95%CI [0.09;0.87]). Moreover, higher levels of IL-4 and IL-2 were associated with a higher MSWC (p inverted question mark= inverted question mark0.01, 95%CI [0.17;0.89] and p inverted question mark= inverted question mark0.02, 95%CI [0.09;0.87] respectively). Clinical characteristics and smoking history were not associated with MSWC, cell proliferation index or MMP and cytokines levels. Finally, we showed an association of the MSWC of bronchial and corresponding bronchiolar epithelial cells obtained from the same patients (p inverted question mark= inverted question mark0.02, 95%CI [0.12;0.89]).ConclusionOur results showed an abnormal bronchial epithelial wound closure process in severe COPD. Further studies are needed to elucidate the contribution and the regulation of this mechanism in the complex pathophysiology of COPD.
Référence
Respir Res. 2014 Nov 27;15(1):151.