RT Journal Article
SR Electronic
T1 Aberrant airway epithelial differentiation resulting from cigarette smoke exposure leads to loss of constitutive antimicrobial peptide and protein (AMP) expression
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA1819
DO 10.1183/13993003.congress-2016.PA1819
VO 48
IS suppl 60
A1 Hiemstra, Pieter S.
A1 Amatngalim, Gimano D.
A1 Schrumpf, Jasmijn A.
A1 Dishchekenian, Fernanda
A1 Mertens, Tinne C.J.
A1 Ninaber, Dennis K.
A1 van der Linden, Abraham C.
A1 Taube, Christian
A1 van der Does, Anne M.
YR 2016
UL https://publications.ersnet.org//content/48/suppl_60/PA1819.abstract
AB Respiratory infections are a major health burden in smokers, and contribute to exacerbations, development and progression of chronic obstructive pulmonary disease (COPD). The mechanisms underlying the increased susceptibility of smokers with or without COPD to these infections can be attributed in part to disrupted mucociliary clearance by the airway epithelium. Currently it is incompletely understood how cigarette smoke (CS) affects production of constitutively expressed AMPs, an important contributor to epithelial antimicrobial barrier function. We hypothesized that CS-induced alterations in epithelial differentiation result in a decrease in constitutively expressed AMPs, thus rendering the host more susceptible to infection.To investigate this, primary bronchial epithelial cells (PBEC;n=7) were cultured at the air-liquid interface and daily exposed to CS for 2-3 weeks. Markers of basal and luminal epithelial cells and AMPs were assessed by qPCR, ELISA and immunofluorescence. Results showed that PBEC differentiation into luminal cells was significantly (p<0.05) compromised by CS. Marked differences in AMPs expression by luminal and basal epithelial cells were detected, indicating their polarized expression in the airway epithelial layer. CS thereby significantly limited the presence of AMPs that are expressed by these luminal epithelial cells. In summary, these new findings highlight the importance of airway epithelial cell differentiation in host defence against microbes.Supported by a Marie Curie Intra-European Fellowship (#622815), Galapagos N.V and the Lung Foundation Netherlands (grant # 5.1.13.033).