Externalized phosphatidylinositides on apoptotic cells are eat-me signals recognized by CD14

Autor: Ok-Hee Kim, Geun-Hyung Kang, June Hur, Jinwook Lee, YunJae Jung, In-Sun Hong, Hookeun Lee, Seung-Yong Seo, Dae Ho Lee, Cheol Soon Lee, In-Kyu Lee, Susan Bonner-Weir, Jongsoon Lee, Young Joo Park, Hyeonjin Kim, Steven E. Shoelson, Byung-Chul Oh
Rok vydání: 2022
Předmět:
Zdroj: Cell Death & Differentiation. 29:1423-1432
ISSN: 1476-5403
1350-9047
DOI: 10.1038/s41418-022-00931-2
Popis: 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)P3antibody, 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 ofCd14−/−than WT mice, especially after induction of apoptosis. Our findings reveal exofacial PIPs to be previously unknown cell death signals recognized by CD14+phagocytes.
Databáze: OpenAIRE
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