Bronchial platelet-activating factor receptor in chronic obstructive pulmonary disease

Reetika Suri,Patrick Mallia,Joanne E Martin,Joseph Footitt,Jie Zhu,Maria-Belen Trujillo-Torralbo,Sebastian L Johnston,Jonathan Grigg

doi:10.1016/j.rmed.2014.03.003

Abstract

Bacteria expressing phosphorylcholine (ChoP) co-opt host-expressed platelet-activating factor receptor (PAFR) to adhere to lower airway cells. Cigarette smoke and rhinovirus (RV) infection upregulate PAFR-dependent bacterial adhesion to airway cells in vitro, and in healthy adults smoking increases the proportion of PAFR positive bronchial epithelial cells. To date the effect of chronic obstructive pulmonary disease (COPD) on smoke-induced PAFR is unknown. We therefore sought to test the hypothesis that bronchial PAFR mRNA expression is increased in smokers with chronic obstructive pulmonary disease (COPD), and further increases after RV infection. Endobronchial biopsies were obtained by fibreoptic bronchoscopy from healthy non-smokers, smokers without airway obstruction, and smokers with COPD, before and after infection with rhinovirus (RV) serotype 16. Endobronchial PAFR mRNA expression was assessed by quantitative PCR and expressed as a ratio of glyceraldehyde-3-phosphate dehydrogenase. The distribution of PAFR was assessed by immunohistochemistry. Baseline PAFR mRNA expression was increased (p < 0.05) in smokers (n = 16), and smokers with COPD (n = 14) compared with non-smokers (n = 18). In RV16 infected subjects there was no increase in PAFR mRNA expression in either non-smokers (n = 9), smokers (n = 8), or smokers with COPD (n = 7). PAFR immunoreactivity in all 3 groups was predominately restricted to the bronchial epithelium and submucosal glands. Endobronchial PAFR mRNA is increased in both smokers without airway obstruction and smokers with COPD. We found preliminary evidence that RV16 infection does not increase PAFR mRNA expression in either smokers or smokers with COPD.

Highlights

MethodsExacerbations of chronic obstructive pulmonary disease (COPD) result from an interaction between external factors such as smoking and viral infection, and host innate immune responses [1]
Wilkinson et al [2] for example, reported that 20% of COPD exacerbations are associated with a rhinovirus (RV) infection, and patients with both RV and bacterial infection have increased airway inflammation and poorer clinical outcomes [2,25]
In the only other study using human lung tissue, Shirasaki et al [11] reported decreased platelet-activating factor receptor (PAFR) mRNA expression in peripheral lung biopsy specimens in 4 smokers compared with 8 controls and no PAFR mRNA expression on airway epithelial cells e the major site for clinically relevant bacterial adhesion

Summary

Methods

Exacerbations of chronic obstructive pulmonary disease (COPD) result from an interaction between external factors such as smoking and viral infection, and host innate immune responses [1]. A wide range of stimuli have been reported to increase PAFR-dependent adhesion of ChoP-expressing bacteria to airway epithelial cells. These include acid [8], interleukin 1a [5], RV infection [9], and cigarette smoke [10,14]. In the only other study using human lung tissue, Shirasaki et al [11] reported decreased PAFR mRNA expression in peripheral lung biopsy specimens in 4 smokers compared with 8 controls and no PAFR mRNA expression on airway epithelial cells e the major site for clinically relevant bacterial adhesion.

Results

Discussion

Conflict of interest statement