Abstract
It is currently unknown how cigarette smoke-induced airway remodelling affects highly expressed respiratory epithelial defence proteins and thereby mucosal host defence.
Localisation 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 exposed daily 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.
Expression of the polymeric immunoglobulin receptor, secretory leukocyte protease inhibitor and long and short PLUNC (palate, lung and nasal epithelium clone protein) was restricted to luminal cells and exposure of differentiating PBECs 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 transepithelial transport of IgA and bacterial killing.
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 chronic obstructive pulmonary disease to respiratory infections.
Abstract
高度表达宿主防御蛋白质的损失a result of cigarette smoke-induced airway epithelial remodellinghttp://ow.ly/Q6Jr30iR6Jg
Footnotes
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Author contributions: Conception and design: G.D. Amatngalim, J.A. Schrumpf, F. Dishchekenian, P.S. Hiemstra, A.M. van der Does; analysis and interpretation: G.D. Amatngalim, J.A. Schrumpf, F. Dishchekenian, T.C.J. Mertens, D.K. Ninaber, A.C. van der Linden, C. Pilette, P.S. Hiemstra, A.M. van der Does; and drafting the manuscript for important intellectual content: G.D. Amatngalim, J.A. Schrumpf, C. Pilette, C. Taube, P.S. Hiemstra, A.M. van der Does.
Conflict of interest: P. Hiemstra reports grants (research fellowship) from the European Union (Marie Curie Intra-European Fellowship), and grants (unrestricted research grant) from Lung Foundation Netherlands, Galapagos N.V. and Boehringer Ingelheim, outside the submitted work.
Support statement: This work was supported by a Marie Curie Intra-European Fellowship (#622815), and grants from the Lung Foundation of the Netherlands (#5.1.13.033) and Galapagos N.V. Funding information for this article has been deposited with theCrossref Funder Registry.
- ReceivedMay 17, 2017.
- AcceptedFebruary 28, 2018.
- Copyright ©ERS 2018