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

Grabiec, Aleksander M.; Hussell, Tracy

In healthy murine and human lungs, airway macrophages make up 95 % of cells retrieved by bronchoalveolar lavage [2, 61] . They exist in a tolerant state due to interaction with proteins and receptors expressed by or secreted from the respiratory epithelium. Furthermore, mucus bathing the epithelium contains surfactant proteins that dampen macrophage responsiveness in health [62] . Chimeric mouse experiments show that resident airway macrophages have an unusually prolonged life span with negligible turnover even at 8 months in the absence of inflammation. This situation changes following their depletion during inflammation where replenishment from the periphery occurs, leading to a population of macrophages that are reported to have a shorter life span. Airway macrophage removal by irradiation leads to replenishment from the periphery and a higher turnover rate of approximately 30 days [63] . However, the fate of resident airway macrophages following pulmonary infection is not entirely clear. One study shows that macrophages recruited to the Fig. 1 The many roles of apoptotic cell recognition and phagocytosis in immunity and infection. a Efferocytosis leads to removal of apoptotic cells without release of their content. When apoptotic cells are not engulfed in a timely manner, they undergo secondary necrosis and release necrotic cell debris which subsequently causes uncontrolled inflammatory activation of the innate immune system by the released 'damage associated molecular patterns' (DAMPS). b During apoptosis, cells expose phosphatidylserine (PtdSer) on the outer leaflet of their membranes, which is recognised by specific receptors expressed on phagocytes. Recognition of PtdSer by TAM receptors through bridging molecules Gas6 and Protein S triggers a signalling cascade which converges on upregulation of suppressor of cytokine signalling-1 and 3 (SOCS3), which act as negative regulators of the immune response.