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About the Authors:
Fabienne Gally
Affiliation: Pulmonary Division, Department of Medicine, National Jewish Health, Denver, Colorado, United States of America
Hong Wei Chu
Affiliation: Pulmonary Division, Department of Medicine, National Jewish Health, Denver, Colorado, United States of America
Russell P. Bowler
* E-mail: [email protected]
Affiliation: Pulmonary Division, Department of Medicine, National Jewish Health, Denver, Colorado, United States of America
Introduction
Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by an abnormal lung inflammatory response to cigarette smoke (CS) that leads to tissue destruction and airflow obstruction [1]. Acute exacerbations, mainly caused by bacterial and viral infections, are a major cause of hospitalization and death. The health care costs are a serious economic burden [2] and negatively impact patient's quality of life. COPD patients have been shown to be more susceptible to infections than “healthy” smokers [3], [4], [5]. Smoking appears to dampen innate immune responses, and as a consequence, pathogens proliferate and persist in the airways of COPD patients [6]. Pseudomonas aeruginosa (P. aeruginosa) represents 5–10% of the pathogens that colonize COPD lungs [7], [8] and is not only involved in acute exacerbations, but also contributes to the chronic process of the disease [9]. In addition, several studies have shown that P. aeruginosa is the cause of more infections as severity of COPD increases [10], [11], [12].
Located at the interface between the host and the environment, the airway epithelium represents the first line of host defense against pathogens or irritants (e.g., CS). The protective role of the epithelium includes recognition of potentially dangerous particulates and microbes [13], as well as production of various mediators such as proinflammatory cytokines (e.g., interleukin-8, IL-8), mucins, and antimicrobial substances (e.g., β defensin-2) [14]. Production of these inflammatory cytokines and antimicrobial substances is tightly regulated. However, persistent and repeated infections in COPD patients suggest an abnormal epithelial cell function [15], [16].
In previous work using Caenorhabditis elegans, we identified the lipid binding protein 7 (lbp-7) to be down regulated after CS exposure and to play a role in innate immunity [17]. The human orthologue of this protein, the fatty acid binding proteins 5 (FABP5), is highly expressed in primary normal human bronchial epithelial (NHBE) cells but is down regulated in COPD patients [17]. Fatty acid binding proteins...