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

Grabiec, Aleksander M.; Hussell, Tracy

While these reports provide clear evidence that removal of apoptotic cells is defective in asthma, in particular in certain disease subtypes, additional studies are needed to characterise the molecular mechanisms underlying the observed defects. Even though potential changes in expression and function of receptors recognising apoptotic cells on airway macrophages have not been formally studied in asthma, it is important to note that the TIM receptor family member TIM-1, which is preferentially expressed on specific lymphocyte populations, is an important susceptibility gene for allergic asthma [102] . Targeting TIM-1 modulates airway inflammation in mouse models of airway hyper-responsiveness at least in part through TIM-1-dependent interaction of NKT cells with PtdSer on the surface of apoptotic cells [103, 104] . These observations suggest that recognition of PtdSer by immune cells that do not phagocytose apoptotic cells also has profound effects on the development of chronic lung inflammation. They also indicate that future studies of molecules involved in apoptotic cell binding in asthma should not be restricted to analyses of airway macrophages as the main contributors to apoptotic cell clearance from the inflamed airways. Interestingly, not only efferocytosis but also engulfment of bacteria by airway macrophages is impaired in asthma [105] . This finding indicates that alterations in the intracellular molecular machinery regulating phagocytosis rather than changes in expression of receptors recognising apoptotic cells might be responsible for the observed phagocytosis defects.