Neutrophil adhesion molecules in experimental rhinovirus infection in COPD

Patrick Mallia,Malcolm Johnson,Simon D Message,Luminita A Stanciu,Sebastian L Johnston,Alberto Papi,Vasile Laza-Stanca,Sarah Elkin,Aurica Telcian,Marco Contoli,Onn M Kon,Katrina K Gray

doi:10.1186/1465-9921-14-72

Abstract

BackgroundCOPD exacerbations are associated with neutrophilic airway inflammation. Adhesion molecules on the surface of neutrophils may play a key role in their movement from blood to the airways. We analysed adhesion molecule expression on blood and sputum neutrophils from COPD subjects and non-obstructed smokers during experimental rhinovirus infections.MethodsBlood and sputum were collected from 9 COPD subjects and 10 smoking and age-matched control subjects at baseline, and neutrophil expression of the adhesion molecules and activation markers measured using flow cytometry. The markers examined were CD62L and CD162 (mediating initial steps of neutrophil rolling and capture), CD11a and CD11b (required for firm neutrophil adhesion), CD31 and CD54 (involved in neutrophil transmigration through the endothelial monolayer) and CD63 and CD66b (neutrophil activation markers). Subjects were then experimentally infected with rhinovirus-16 and repeat samples collected for neutrophil analysis at post-infection time points.ResultsAt baseline there were no differences in adhesion molecule expression between the COPD and non-COPD subjects. Expression of CD11a, CD31, CD62L and CD162 was reduced on sputum neutrophils compared to blood neutrophils. Following rhinovirus infection expression of CD11a expression on blood neutrophils was significantly reduced in both subject groups. CD11b, CD62L and CD162 expression was significantly reduced only in the COPD subjects. Blood neutrophil CD11b expression correlated inversely with inflammatory markers and symptom scores in COPD subjects.ConclusionFollowing rhinovirus infection neutrophils with higher surface expression of adhesion molecules are likely preferentially recruited to the lungs. CD11b may be a key molecule involved in neutrophil trafficking in COPD exacerbations.

Highlights

Chronic obstructive pulmonary disease (COPD) is a growing global epidemic and its prevalence is expected to increase markedly in the future [1]
Neutrophil markers at baseline Surface markers were initially measured on blood and sputum neutrophils at baseline prior to rhinovirus infection in the stable state
No significant differences in expression of any marker were found between the groups on either blood or sputum neutrophils

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a growing global epidemic and its prevalence is expected to increase markedly in the future [1]. Acute exacerbations (macrophage associated antigen-1) and transmigration through the endothelial monolayer involves CD31 (platelet endothelial cell adhesion molecule-1) [5]. Other molecules including CD54 (intercellular adhesion molecule-1 (ICAM-1)) are involved in neutrophil transmigration but their exact role is undetermined. The role of specific adhesion molecules in neutrophil recruitment in vivo in COPD has not been established. Neutrophilic inflammation in COPD is poorly responsive to corticosteroids, so different anti-inflammatory approaches are needed and inhibition of adhesion molecules is one such approach that merits exploration [6]. COPD exacerbations are associated with neutrophilic airway inflammation. Adhesion molecules on the surface of neutrophils may play a key role in their movement from blood to the airways. We analysed adhesion molecule expression on blood and sputum neutrophils from COPD subjects and non-obstructed smokers during experimental rhinovirus infections

Methods

Results

Conclusion