Engulfment of apoptotic cells involves the redistribution of membrane phosphatidylserine on phagocyte and prey

D Marguet, MF Luciani, A Moynault, P Williamson… - Nature cell …, 1999 - nature.com
D Marguet, MF Luciani, A Moynault, P Williamson, G Chimini
Nature cell biology, 1999nature.com
* Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, Case 906, 13288 Marseille
Cedex 09, France† Department of Biology, Amherst College, Amherst, Massachussetts
01002, USA‡ e-mail: chimini@ ciml. univ-mrs. fr he clearance of cells that are dying by
apoptosis is essential to the control of tissue homeostasis1. In contrast to classical models of
phagocytosis, the molecular dissection of engulfment of apoptotic cells is still preliminary1.
Genetic approaches in Caenorhabditis elegans have yielded several mutants, characterized …
* Centre d’Immunologie INSERM-CNRS de Marseille-Luminy, Case 906, 13288 Marseille Cedex 09, France† Department of Biology, Amherst College, Amherst, Massachussetts 01002, USA‡ e-mail: chimini@ ciml. univ-mrs. fr he clearance of cells that are dying by apoptosis is essential to the control of tissue homeostasis1. In contrast to classical models of phagocytosis, the molecular dissection of engulfment of apoptotic cells is still preliminary1. Genetic approaches in Caenorhabditis elegans have yielded several mutants, characterized by the persistence of apoptotic corpses2–5. In mammals, in vitro studies have mostly shed light on the macrophage receptors engaged in the recognition of apoptotic surfaces1, 6. Both of these approaches highlighted the importance of an ATP-binding cassette (ABC)-type transporter, named CED-7 in C. elegans and ABC1 in mouse4, 7. The requirement for ABC1 on the macrophage surface is specific to the engulfment7. Here we assess the distinctive features of engulfment in comparison with other forms of phagocytosis, and find that engulfment exhibits a unique sensitivity to the ABC1 blocker glyburide8. In addition, glyburide, as well as antimycin and oligomycin, affects membrane behaviour in both partners of engulfment: when applied to either phagocyte or prey, these drugs impair the Ca2+-induced transmembrane randomization of phospholipids9. Our results show that engulfment requires a symmetrical transbilayer movement of lipids across the membranes of both the phagocyte and the prey.
To differentiate the engulfment from classical forms of phagocytosis, we analysed the effect of pretreatment of mouse macrophages with classical inhibitors of phagocytosis10. The phagocytosis of opsonized sheep red blood cells and of apoptotic thymocytes exhibited similar sensitivity to cytochalasin D, lysosomotropic agents, cytosolic acidification, inhibitors of protein kinase C, and nocodazole (Fig. 1A).
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