Abstract
Rationale: Chronic Obstructive Pulmonary Disease (COPD) is characterized by an excessive activation of the adaptive immune system and uncontrolled expansion of the B-cell pool. A PRoliferation-Inducing Ligand (APRIL) is a key promoter of B cell expansion. APRIL has been strongly linked to non small cell lung cancer (NSCLC) development, but little is known about its involvement in COPD. Methods: Using immunostaining, APRIL expression was assessed in lung sections from 4 subjects with COPD, 4 subjects with NSCLC, 4 subjects diagnosed with both COPD and NSCLC, 4 smokers (SC) and non-smokers (NSC) without COPD or NSCLC. The number of APRIL-positive B cells, alveolar macrophages (AMs), polymorphonuclear neutrophils (PMNs) in the lung, and alveolar epithelial cells (AECs) was quantified. Result: The number of APRIL-exprressing B cells, AMs, PMNs, and AECs was significantly higher in patients having both COPD and NSCLC than in patients with either COPD or NSCLC alone, SC, or NSC. The number of APRIL-expressing AMs and AECs was higher patients with NSCLC alone than in patients with COPD alone. The number of APRIL-expressing AECs was significantly higher in COPD patients than in SC and NSC. No difference in APRIL expression was found between SC and NSC. Conclusion: APRIL was overexpressed in B cells, AMs, and AECs from the lungs of patients with both COPD and NSCLC than in patients with COPD or NSCLC alone or controls. These findings suggest that APRIL may contribute to the pathogenesis of both COPD and NSCLC, and possibly to the development of NSCLC in patients with established COPD.
Highlights
Chronic Obstructive Pulmonary Disease (COPD) is characterized by an excessive activation of the adaptive immune system and, in particular, uncontrolled expansion of the B-cell pool
COPD was diagnosed on the basis of the presence of emphysema in high resolution computed tomography (HRCT) scans of the thorax and an FEV1/FVC ratio < 0.7, but the FEV1% predicted was not available from the electronic medical records
We report for the first time that there are increases in numbers of A PRoliferation-Inducing Ligand (APRIL)-expressing leukocytes and alveolar epithelial cells (AECs) in lungs of patients with either COPD or non small cell lung cancer (NSCLC) versus control subjects without these diseases
Summary
Chronic Obstructive Pulmonary Disease (COPD) is characterized by an excessive activation of the adaptive immune system and, in particular, uncontrolled expansion of the B-cell pool. APRIL has been strongly linked to non small cell lung cancer (NSCLC) onset and progression previously. COPD patients have an increased risk of developing non-small cell lung cancer (NSCLC) that is independent of smoking pack-year history [1, 2]. Increased lung oxidative stress levels can increase the susceptibility of COPD patients to recurrent respiratory tract infections, and drive chronic inflammation in the lungs, leading to further DNA damage and cellular injury by inducing the production of cytokines and proteinases in the lung [5]. Injury to the lungs that is induced by chronic inflammation triggers repair processes including cellular proliferation which, together with ROS and RNS-induced DNA damage, may promote tumorigenesis
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