Supplementing Defect in Club Cell Secretory Protein Attenuates Airway Inflammation in COPD

Anne-Sophie Gamez (1) , Delphine Gras (1) , Aurélie Petit (1) , Lucie Knabe (2, 3) , Nicolas Molinari (2, 3) , Isabelle Vachier (1) , Pascal Chanez (4, 5) , Arnaud Bourdin (2, 3)

1 Département pneumologie et addictologie [Montpellier]
2 PhyMedExp - Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046]
3 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
4 URPE - Unité des Rickettsies et pathogènes émergents
5 AMU - Aix Marseille Université

BACKGROUND Club cell secretory protein (CCSP) is a protective biomarker associated with annual decline in lung function. COPD progression results from an imbalance between injury and repair initially triggered by cigarette smoking. OBJECTIVE We investigated the effect of CCSP as a therapeutic strategy to restore the balance between injury and repair in COPD simultaneously, validating an ex vivo air-liquid interface (ALI) culture of human bronchial epithelial cells. METHODS Endobronchial biopsy specimens (EBBs) were obtained from 13 patients with COPD, eight smokers, and eight control subjects. Morphometric analysis of the initial EBBs was performed. ALI cultures derived from the same EBBs were exposed to cigarette smoke extract (CSE) with or without exogenous recombinant human CCSP (rhCCSP) supplementation. CCSP and IL-8 concentrations were assessed at steady state and after CSE exposure. RESULTS Morphometric analysis of the initial EBBs showed increased cell density but decreased immunostaining of CCSP+ cells in EBBs of patients with COPD (P = .03 vs control subjects). At steady state, lower CCSP (P = .04) and higher IL-8 levels (P < .0001) were found in COPD ALI epithelium. Exogenous rhCCSP supplementation dampened CSE-induced IL-8-release in patients with COPD and returned to levels similar to those of smokers and control subjects (P = .0001). A negative correlation was found between IL-8-release in ALI and CCSP+ cell density in initial biopsy specimens (P = .0073). CONCLUSIONS In vitro, rhCCSP exogenous supplementation can reverse CSE-induced IL-8 release in biopsy specimens from patients with COPD, indicating a potential use of this strategy in vivo.

Domaines: Sciences du Vivant [q-bio]

Anne-Sophie Gamez, Delphine Gras, Aurélie Petit, Lucie Knabe, Nicolas Molinari, et al.. Supplementing Defect in Club Cell Secretory Protein Attenuates Airway Inflammation in COPD. Chest, 2015, 147 (6), pp.1467 - 1476. ⟨10.1378/chest.14-1174⟩. ⟨hal-01756118⟩