Aberrant epithelial differentiation by cigarette smoke dysregulates respiratory host defence

Gimano D Amatngalim, Jasmijn A Schrumpf, Fernanda Dishchekenian, Tinne C J Mertens, Dennis K Ninaber, Abraham C van der Linden, Charles Pilette, Christian Taube, Pieter S Hiemstra, Anne M van der Does

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Article number1701009
JournalEuropean Respiratory Journal
Issue number4
Early online date2018
Publication statusPublished - Apr 2018


  • Journal Article
  • Gene Expression/drug effects
  • Microscopy, Confocal
  • Cell Differentiation/drug effects
  • Tobacco Products/toxicity
  • Epithelial Cells/cytology
  • Humans
  • Cells, Cultured
  • Bronchi/cytology
  • Smoke
  • Immunoglobulin A/immunology


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