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

Grabiec, Aleksander M.; Hussell, Tracy

PtdSer and other 'eat-me' signals exposed on apoptotic cells bind a plethora of receptors on phagocytic cells, a number of which have been identified in the lung (Table 1) . Externalised PtdSer is recognised directly by triggering receptor expressed by myeloid cells-2 (TREM2) [30] , CD300 [31] , receptor for advanced glycation end products (RAGE) [32] , stabilin-2 [33] , brain-specific angiogenesis inhibitor-1 (BAI1) [34] and the family of T cell/transmembrane, immunoglobulin, and mucin (TIM) receptors, which includes TIM-1, 3 and 4 [35, 36] . Other engulfment receptors require bridging molecules to link them to externalised PtdSer. For example, integrin αvβ3 or αvβ5 requires MFG-E8, while Tyro3, Axl and MerTK that form the TAM receptor tyrosine kinase family [37] require the bridging molecules Protein S or growth arrest specific 6 (Gas6) [38] . The N-terminal Gla domains of Protein S and Gas6 bridge TAM receptors to PtdSer on the surface of apoptotic cells [39] , whereas the C-terminal sex hormone-binding globulin-like domains bind and activate the TAM receptor [40] . There are also a number of receptors that recognise other externalised ligands including scavenger receptor class F, member 1 (SCARF1) and LDL receptorrelated protein-1 (LRP-1, also known as CD91) that recognise C1q and calreticulin, respectively, CD36 together with integrin αvβ3 or αvβ5 that recognises TSP-1, CD14 that binds a modified form of the intracellular adhesion molecule ICAM3, and lectin receptors that recognise altered sugars [1] .