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

Grabiec, Aleksander M.; Hussell, Tracy

Collectively, the data from patients with asthma, COPD, CF and pulmonary fibrosis indicate that defective apoptotic cell clearance in lung diseases is not specific for individual diagnoses but rather represents a general hallmark of chronic inflammation. Although several mechanisms contributing to these defects have been proposed, it remains to be verified whether impairment of efferocytosis might be a direct cause of chronic inflammation, or is a consequence to the ongoing inflammatory processes that contributes to chronicity and prevents resolution. The latter model is supported by the observation that mice lacking the TAM receptor Axl do not develop spontaneous lung inflammation despite defects in apoptotic cell uptake by airway macrophages [2] , but more detailed analyses of regulation and function of PtdSer recognition receptors in the human lung are required. Finally, because recognition of apoptotic cells by PtdSer-recognising receptors activates downstream signalling pathways even without engulfment [46] , future studies are needed to verify whether activation of transcriptional programmes triggered by recognition of apoptotic cells is also altered in chronic lung diseases and, if so, how they can be manipulated in the clinic by specific modulators of PtdSer recognition receptors.