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

Grabiec, Aleksander M.; Hussell, Tracy

Asthma is an obstructive airway disease characterised by hyper-responsiveness and chronic inflammation of the respiratory tract. While neutrophils are a predominant cell type in the lungs of COPD patients, asthma represents eosinophildominant airway inflammation. Initial priming of the adaptive immune system by airway allergens leads to the activation of tissue-resident mast cells, which release a broad array of inflammatory mediators promoting migration of eosinophils into the airways [92] . Products of eosinophil degranulation, including major basic protein, eosinophil cationic protein and reactive oxygen species, are cytotoxic to epithelial cells and cause airway damage and tissue remodelling. Indeed, increased numbers of apoptotic epithelial cells have been detected in the lungs of patients with asthma compared to healthy individuals [93] . Apoptosis and subsequent uptake by phagocytes appear to be a predominant mechanism of eosinophil removal from the airways [94, 95] , and glucocorticoids, which are commonly used to control inflammation in asthma, induce eosinophil apoptosis [96] . These observations indicate that high efficiency of the phagocytic system is required for removal of large quantities of apoptotic eosinophils and bronchial epithelial cells from the airways of patients with asthma and raise the possibility that defects in efferocytosis might prevent resolution of lung inflammation.