PT - JOURNAL ARTICLE AU - Lucie Knabe AU - Aurélie Petit AU - Charlotte Vernisse AU - Jérémy Charriot AU - Martine Pugnière AU - Corinne Henriquet AU - Souphatta Sasorith AU - Nicolas Molinari AU - Pascal Chanez AU - Jean-Philippe Berthet AU - Carey Suehs AU - Isabelle Vachier AU - Engi Ahmed AU - Arnaud Bourdin TI - CCSP counterbalances airway epithelial-driven neutrophilic chemotaxis AID - 10.1183/13993003.02408-2018 DP - 2019 Jan 01 TA - European Respiratory Journal PG - 1802408 4099 - http://erj.ersjournals.com/content/early/2019/04/05/13993003.02408-2018.short 4100 - http://erj.ersjournals.com/content/early/2019/04/05/13993003.02408-2018.full AB - CCSP knockout mice exhibit increased airway neutrophilia, as found in COPD. We therefore investigated whether treating COPD airway epithelia with 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 their supernatants were assessed by Dunn chambers. Neutrophil chemotaxis along rhIL8 gradients (with/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. rhIL-8 induced chemotaxis of neutrophils was reduced by rhCCSP. rhCCSP and rhIL8 co-immunoprecipitated. SPR confirmed this in vitro interaction (KD=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=.746, p<.001).CCSP is a biologically relevant counter-balancer of neutrophil chemotactic activity. Altogether, these different approaches suggest that among the possible mechanisms involved, CCSP may directly neutralise IL8.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Knabe has nothing to disclose.Conflict of interest: Dr. Petit has nothing to disclose.Conflict of interest: Ms Vernisse has nothing to disclose.Conflict of interest: Dr. Charriot has nothing to disclose.Conflict of interest: Dr. Pugnière has nothing to disclose.Conflict of interest: Ms Henriquet has nothing to disclose.Conflict of interest: Dr. Sasorith has nothing to disclose.Conflict of interest: Dr. Molinari has nothing to disclose.Conflict of interest: Dr. Chanez has nothing to disclose.Conflict of interest: Dr. Berthet has nothing to disclose.Conflict of interest: Dr. Suehs has nothing to disclose.Conflict of interest: Dr. Vachier has nothing to disclose.Conflict of interest: Ms Ahmed has nothing to disclose.Conflict of interest: Dr. Bourdin has nothing to disclose.