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

Grabiec, Aleksander M.; Hussell, Tracy

Cystic fibrosis (CF) is a heritable disorder caused by mutation in the CF transmembrane conductance regulator (CFTR) and characterised by severe pulmonary manifestations. Impaired mucociliary clearance in CF patients prevents elimination of bacteria from the lung, leading to persistent neutrophilic inflammation and progressive, irreversible damage of the airways [107] . Similar to other lung diseases associated with chronic inflammation, both accumulation of apoptotic cells in the airways and reduced numbers of phagocytic bodies within sputum macrophages are observed in patients with CF compared to control patients with chronic bronchitis [25] . Mechanistically, degranulation products of immune cells are partly responsible for efferocytosis defects in CF as neutrophil elastase present in the airway fluid of CF patients selectively cleaves PtdSer recognition receptors and suppresses apoptotic cell removal by airway macrophages [25] . Other potential mechanisms contributing to impaired apoptotic cell clearance in CF involve the release of HMGB1 which, similar to COPD, is elevated in sputum samples from CF patients [108] and effects of bacterial products on airway macrophages. Pseudomonas aeruginosa infections are common in CF and represent an important cause of mortality in CF lung manifestations. In vitro, P. aeruginosa toxic metabolite pyocyanin and the polysaccharide alginate inhibit apoptotic cell uptake by macrophages [109, 110] , though the relevance of this mechanism in patients has yet to be demonstrated. Interestingly, animal studies indicate that airway epithelial cells in CF might also be deficient in phagocytic functions.