Externalized phosphatidylinositides on apoptotic cells are eat-me signals recognized by CD14
- Authors
- Kim, Ok-Hee; Kang, Geun-Hyung; Hur, June; Lee, Jinwook; Jung, YunJae; Hong, In-Sun; Lee, Hookeun; Seo, Seung-Yong; Lee, Dae Ho; Lee, Cheol Soon; Lee, In-Kyu; Bonner-Weir, Susan; Lee, Jongsoon; Park, Young Joo; Kim, Hyeonjin; Shoelson, Steven E.; Oh, Byung-Chul
- Issue Date
- Jul-2022
- Publisher
- SPRINGERNATURE
- Citation
- CELL DEATH AND DIFFERENTIATION, v.29, no.7, pp.1423 - 1432
- Journal Title
- CELL DEATH AND DIFFERENTIATION
- Volume
- 29
- Number
- 7
- Start Page
- 1423
- End Page
- 1432
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/84745
- DOI
- 10.1038/s41418-022-00931-2
- ISSN
- 1350-9047
- Abstract
- 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)P-3 antibody, AKT- and PLC delta 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.
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