Format

Send to

Choose Destination
Eur Respir J. 2019 Jul 11;54(1). pii: 1802408. doi: 10.1183/13993003.02408-2018. Print 2019 Jul.

CCSP counterbalances airway epithelial-driven neutrophilic chemotaxis.

Author information

1
PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, Montpellier, France.
2
Dept of Respiratory Diseases, CHU Montpellier, University of Montpellier, Montpellier, France.
3
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut Régional du Cancer de Montpellier, Montpellier, France.
4
Laboratoire de Génétique Moléculaire, CHU Montpellier, University of Montpellier, Montpellier, France.
5
IMAG U5149, Dept of Medical Information, CHU Montpellier, University of Montpellier, Montpellier, France.
6
C2VN - INSERM U1263 INRA 1260, AP-HM, Dept of Respiratory Diseases, Aix Marseille University, Marseille, France.
7
Dept of Thoracic Surgery, CHU Montpellier, University of Montpellier, Montpellier, France.
8
PhyMedExp, University of Montpellier, INSERM U1046, CNRS UMR 9214, Montpellier, France a-bourdin@chu-montpellier.fr.

Abstract

Club cell secretory protein (CCSP) knockout mice exhibit increased airway neutrophilia, as found in chronic obstructive pulmonary disease (COPD). We therefore investigated whether treating COPD airway epithelia with recombinant human CCSP (rhCCSP) could dampen exaggerated airway neutrophilia.Control, smoker and COPD air-liquid interface (ALI) cultures exposed to cigarette smoke extract (CSE) were treated with and without rhCCSP. The chemotactic properties of the supernatants were assessed using Dunn chambers. Neutrophil chemotaxis along recombinant human interleukin 8 (rhIL8) gradients (with and without rhCCSP) was also determined. rhCCSP-rhIL8 interactions were tested through co-immunoprecipitation, Biacore surface plasmon resonance (SPR) and in silico modelling. The relationship between CCSP/IL8 concentration ratios in the supernatant of induced sputum from COPD patients versus neutrophilic airway infiltration assessed in lung biopsies was assessed.Increased neutrophilic chemotactic activity of CSE-treated ALI cultures followed IL8 concentrations and returned to normal when supplemented with rhCCSP. rhIL8-induced chemotaxis of neutrophils was reduced by rhCCSP. rhCCSP and rhIL8 co-immunoprecipitated. SPR confirmed this in vitro interaction (equilibrium dissociation constant=8 µM). In silico modelling indicated that this interaction was highly likely. CCSP/IL8 ratios in induced sputum correlated well with the level of small airway neutrophilic infiltration (r2=0.746, p<0.001).CCSP is a biologically relevant counter-balancer of neutrophil chemotactic activity. These different approaches used in this study suggest that, among the possible mechanisms involved, CCSP may directly neutralise IL8.

Conflict of interest statement

Conflict of interest: L. Knabe has nothing to disclose. Conflict of interest: A. Petit has nothing to disclose. Conflict of interest: C. Vernisse has nothing to disclose. Conflict of interest: J. Charriot has nothing to disclose. Conflict of interest: M. Pugnière has nothing to disclose. Conflict of interest: C. Henriquet has nothing to disclose. Conflict of interest: S. Sasorith has nothing to disclose. Conflict of interest: N. Molinari has nothing to disclose. Conflict of interest: P. Chanez has nothing to disclose. Conflict of interest: J-P. Berthet has nothing to disclose. Conflict of interest: C. Suehs has nothing to disclose. Conflict of interest: I. Vachier has nothing to disclose. Conflict of interest: E. Ahmed has nothing to disclose. Conflict of interest: A. Bourdin has nothing to disclose.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center