The Impact of Defective Clearance of Apoptotic Cells in the Pathogenesis of Chronic Lung Diseases: Chronic Obstructive Pulmonary Disease, Asthma and Cystic Fibrosis

Abstract

Apoptosis is an important process in the regulation of cell turnover and inflammatory responses in the lungs. Efficient clearance of apoptotic cells is a critical component of the process to avoid accumulation of apoptotic material and the subsequent development of secondary necrosis and incitement or perpetuation of inflammation. Airway and alveolar macrophages have the major role in ensuring effective clearance, but other cells including airway epithelial cells also have a role. Several recent studies have identified defects in the phagocytic capacity of macrophages obtained from subjects with chronic pulmonary diseases including chronic obstructive pulmonary disease, asthma and cystic fibrosis. There is evidence that these defects relate to levels of expression of various cell surface receptors including the mannose receptor and components of the collectin system. The defects in macrophage function are a potential target for new therapeutic interventions which may complement existing therapies. Approaches currently being pursued include the use of macrolide antibiotics, statins, exogenous surfactant proteins and mannose binding lectin. Pre-clinical studies and early phase human studies show some promise but further work is needed before these strategies emerge as established therapies.