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Externalized phosphatidylinositides on apoptotic cells are eat-me signals recognized by CD14
Cited 8 time in
Web of Science
Cited 10 time in Scopus
- Authors
- Issue Date
- 2022-07
- Publisher
- Nature Publishing Group
- Citation
- Cell Death and Differentiation, Vol.29 No.7, pp.1423-1432
- Abstract
- © 2022, The Author(s).Apoptotic cells are rapidly engulfed and removed by phagocytes after displaying cell surface eat-me signals. Among many phospholipids, only phosphatidylserine (PS) is known to act as an eat-me signal on apoptotic cells. Using unbiased proteomics, we identified externalized phosphatidylinositides (PIPs) as apoptotic eat-me signals recognized by CD14+ phagocytes. Exofacial PIPs on the surfaces of early and late-apoptotic cells were observed in patches and blebs using anti-PI(3,4,5)P3 antibody, AKT- and PLCδ PH-domains, and CD14 protein. Phagocytosis of apoptotic cells was blocked either by masking exofacial PIPs or by CD14 knockout in phagocytes. We further confirmed that exofacial PIP+ thymocytes increased dramatically after in vivo irradiation and that exofacial PIP+ cells represented more significant populations in tissues of Cd14−/− than WT mice, especially after induction of apoptosis. Our findings reveal exofacial PIPs to be previously unknown cell death signals recognized by CD14+ phagocytes.
- ISSN
- 1350-9047
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