Abstract
Research question: It is currently unknown how cigarette smoke-induced airway remodelling affects highly expressed respiratory epithelial defence proteins and thereby mucosal host defence.
Methods: Localization of a selected set of highly expressed respiratory epithelial host defence proteins was assessed in well-differentiated primary bronchial epithelial cell (PBEC) cultures. Next, PBEC were cultured at the air-liquid interface and during differentiation for 2–3 weeks daily exposed to whole cigarette smoke. Gene expression, protein levels and epithelial cell markers were subsequently assessed. In addition, functional activities and persistence of the cigarette smoke-induced effects upon cessation were determined.
Results: Expression of pIgR, SLPI, long and short PLUNC was restricted to luminal cells and exposure of differentiating PBEC to cigarette smoke resulted in a selective reduction of the expression of these luminal cell-restricted respiratory host defence proteins compared to controls. This reduced expression was a consequence of cigarette smoke-impaired end-stage differentiation of epithelial cells, and accompanied by a significant decreased trans-epithelial transport of IgA and bacterial killing.
Conclusions: These findings shed new light on the importance of airway epithelial cell differentiation in respiratory host defence and could provide an additional explanation for the increased susceptibility of smokers and patients with COPD to respiratory infections.
Abstract
Loss of highly expressed host defence proteins as a result of cigarette smoke-induced airway epithelial remodelling
Footnotes
This 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. Amatngalim has nothing to disclose.
Conflict of interest: Dr. Schrumpf has nothing to disclose.
Conflict of interest: Dr. Dishchekenian has nothing to disclose.
Conflict of interest: Dr. Mertens has nothing to disclose.
Conflict of interest: Dr. Ninaber has nothing to disclose.
Conflict of interest: Dr. van der Linden has nothing to disclose.
Conflict of interest: Dr. Pilette has nothing to disclose.
Conflict of interest: Dr. Taube has nothing to disclose.
Conflict of interest: Dr. Hiemstra reports grants from European Union (Marie Curie Intra-European Fellowship), grants from Lung Foundation Netherlands, grants from Galapagos N.V., during the conduct of the study; grants from Boehringer Ingelheim, outside the submitted work.
Conflict of interest: Dr. van der Does has nothing to disclose.
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