PT  - JOURNAL ARTICLE
AU  - Gimano D. Amatngalim
AU  - Jasmijn A. Schrumpf
AU  - Fernanda Dishchekenian
AU  - Tinne C.J. Mertens
AU  - Dennis K. Ninaber
AU  - Abraham C. van der Linden
AU  - Charles Pilette
AU  - Christian Taube
AU  - Pieter S. Hiemstra
AU  - Anne M. van der Does
TI  - Aberrant epithelial differentiation by cigarette smoke dysregulates respiratory host defence
AID  - 10.1183/13993003.01009-2017
DP  - 2018 Apr 01
TA  - European Respiratory Journal
PG  - 1701009
VI  - 51
IP  - 4
4099  - http://erj.ersjournals.com/content/51/4/1701009.short
4100  - http://erj.ersjournals.com/content/51/4/1701009.full
SO  - Eur Respir J2018 Apr 01; 51
AB  - 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.Loss of highly expressed host defence proteins as a result of cigarette smoke-induced airway epithelial remodelling http://ow.ly/Q6Jr30iR6Jg