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How macrophages deal with death

Abstract

Tissue macrophages rapidly recognize and engulf apoptotic cells. These events require the display of so-called eat-me signals on the apoptotic cell surface, the most fundamental of which is phosphatidylserine (PtdSer). Externalization of this phospholipid is catalysed by scramblase enzymes, several of which are activated by caspase cleavage. PtdSer is detected both by macrophage receptors that bind to this phospholipid directly and by receptors that bind to a soluble bridging protein that is independently bound to PtdSer. Prominent among the latter receptors are the MER and AXL receptor tyrosine kinases. Eat-me signals also trigger macrophages to engulf virus-infected or metabolically traumatized, but still living, cells, and this ‘murder by phagocytosis’ may be a common phenomenon. Finally, the localized presentation of PtdSer and other eat-me signals on delimited cell surface domains may enable the phagocytic pruning of these ‘locally dead’ domains by macrophages, most notably by microglia of the central nervous system.

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Fig. 1: Receptors and ligands mediating apoptotic cell recognition and phagocytosis by macrophages.
Fig. 2: Phosphatidylserine-triggered phagocytic engulfment of living cells.
Fig. 3: Phosphatidylserine-delimited phagocytosis of only small parts of cells.

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Acknowledgements

The author thanks the members of his laboratory for comments and discussions. This work is supported by grants from the US National Institutes of Health (NIH) (AI101400, NS085296 and AG060748), the Cure Alzheimer’s Fund and the Leona M. and Harry B. Helmsley Charitable Trust.

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Nature Reviews Immunology thanks S. Grinstein and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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NIH3T3 cells

A cell line derived from mouse embryonic fibroblasts.

AD293 cells

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Lemke, G. How macrophages deal with death. Nat Rev Immunol 19, 539–549 (2019). https://doi.org/10.1038/s41577-019-0167-y

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