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

Grabiec, Aleksander M.; Hussell, Tracy

Keywords Efferocytosis . Phosphatidylserine . Apoptotic cell clearance . Lung . Airway macrophage . Inflammation Cellular turnover occurs as part of the normal homeostatic process and is vital for the contraction of cells recruited during an inflammatory response [1] . As with most biological processes, it is becoming apparent that turnover of cells is regulated in a tissue-specific manner and this specificity is primarily driven by locally produced factors. For example, the unique microenvironment of the airspaces drives a distinct expression pattern of apoptotic cell recognition receptors on airway macrophages compared to tissue-resident macrophages from other anatomical locations [2] . In the airways, cell turnover is primarily mediated by induction of apoptosis followed by engulfment of apoptotic cells by phagocytes, called 'efferocytosis'. The term 'efferocytosis' was coined to separate engulfment of apoptotic cells from other forms of phagocytosis and derived from the Latin word 'effere' that translates as 'take to the grave'. While phagocytosis of pathogens requires initiation of an inflammatory response, removal of self-cells that undergo apoptosis is a tolerogenic process that prevents excessive inflammation and/or autoimmunity caused by the release of 'damage associated molecular patterns' (DAMPS) from apoptotic cells that are not cleared in a timely manner and undergo secondary necrosis. To achieve this distinction, macrophages and other phagocytes utilise different sets of receptors to recognise microbial particles and cells undergoing apoptosis, activation of which subsequently leads to distinct cell activation programmes. Whereas phagocytosis of pathogens triggers conserved pro-inflammatory signalling pathways, engulfment of apoptotic cells by phagocytes may promote the wound repair process, the production of factors to curtail inflammation or the secretion of growth factors to shape a developing tissue. Efferocytosis therefore leads to different consequences and is a burgeoning focus of research, driven by the discovery of ever more apoptotic cell recognition receptors and, importantly, pathogens that use the apoptotic cell clearance process to facilitate their entry into host cells and/or subvert anti-pathogen immunity.