The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation

Grabiec, Aleksander M.; Hussell, Tracy

The most comprehensive analysis of defects in apoptotic cell clearance has been performed in chronic obstructive pulmonary disease (COPD), which is a chronic lung disease characterised by un-resolving inflammation due to accumulation of activated neutrophils and T cells causing small-airway obstruction, peribronchial fibrosis and/or destruction of airway walls (emphysema). These pathological processes lead to progressive destruction of lung parenchyma and, as a consequence, airflow limitation that is not fully reversible in patients with emphysema, and in other subtypes of COPD [74] . Historically, lung pathology in COPD was attributed to alterations in the protease/anti-protease balance and oxidative stress caused by cigarette smoking, which is the main risk factor for COPD. However, there is evidence that indicates an important role of aberrant apoptosis and apoptotic cell clearance in the lung damage observed in COPD [75] . Several reports demonstrate accumulation of apoptotic epithelial, endothelial and immune cells in the lungs of patients with COPD and/or emphysema [69, 76, 77] , and induction of structural airway cell apoptosis is sufficient to cause emphysematous changes in mice [78] .