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

Grabiec, Aleksander M.; Hussell, Tracy

Initial studies by Hyunh et al. demonstrate that airway macrophages from patients with severe asthma contain reduced numbers of phagocytic bodies compared to healthy donors and patients with mild/moderate asthma and are defective in phagocytosing apoptotic Jurkat T cells in vitro [97] . Failure of airway macrophages from patients with severe asthma to efficiently clear apoptotic cells is associated with reduced production of anti-inflammatory eicosanoids [97] , suggesting that defects in efferocytosis might contribute to perpetuation of inflammation in asthma, not only through secondary necrosis of apoptotic cells, but also by reduced release of regulatory mediators that are normally produced upon recognition of apoptotic cells by airway macrophages. More recently, it has been shown that efferocytosis of apoptotic bronchial epithelial cells by airway macrophages isolated from induced sputum of patients with non-eosinophilic asthma is significantly reduced compared with patients with eosinophilic asthma, and the degree of uptake impairment is comparable to that observed in COPD [98] . This observation might partly explain the persistent neutrophilia and aberrant innate immune responses in this subgroup of patients [99] . Efferocytosis defects in asthma are associated not only with the subtype of airway inflammation but also with the BMI index: airway macrophages from obese patients with asthma, which typically suffer from more severe disease symptoms [100] , are characterised by significantly reduced numbers of phagocytic bodies compared to non-obese asthmatics [101] . Notably, defective efferocytic function in obese asthmatics is not restricted to the site of inflammation as decreased uptake of beads mimicking apoptotic cells is also observed in peripheral blood monocytes isolated from these patients, correlating with reduced glucocorticoid responsiveness [101] .