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

Grabiec, Aleksander M.; Hussell, Tracy

Elevated levels of apoptotic cells and reduced frequencies of phagocytic bodies within bronchoalveolar lavage macrophages have also been reported in patients with idiopathic pulmonary fibrosis (IPF) [112] . IPF is an interstitial lung disease characterised by epithelial injury that is followed by aberrant alveolar wound repair and scar formation, which ultimately lead to respiratory failure and death. IPF is frequently accompanied by chronic neutrophilic inflammation [113] . Interestingly, intratracheal instillation of apoptotic cells ameliorates fibrosis and inflammation in bleomycin-induced lung injury in mice [58, 114] , indicating that signalling triggered by apoptotic cell recognition may play a protective role in lung diseases associated with dysregulated healing processes. The anti-fibrotic effects of apoptotic cells in this model are dependent on the induction of PPARγ expression in airway macrophages and increased production of hepatocyte growth factor (HGF), which plays a key role in alveolar epithelial repair upon lung injury [58, 114] . These observations suggest that defects in efferocytosis in IPF patients may be responsible not only for inefficient clearance of apoptotic cells but also for diminished production of factors that support tissue repair without fibrosis.