Externalized phosphatidylinositides on apoptotic cells are eat-me signals recognized by CD14.
Externalized phosphatidylinositides on apoptotic cells are eat-me signals recognized by CD14.
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凋亡细胞上的外化磷脂酰肌醇是由CD 14识别的eat-me信号。
DOI：
10.1038/s41418-022-00931-2
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发表时间：
2022-07
影响因子：
12.4
通讯作者：
Oh, Byung-Chul
中科院分区：
文献类型：
--
作者：
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
细胞表面出现吞噬信号后，凋亡细胞被吞噬细胞迅速吞噬和清除。在许多磷脂中，只有磷脂酰丝氨酸(PS)被认为是凋亡细胞上的Eat-me信号。利用无偏倚蛋白质组学方法，我们确定外化磷脂酰肌醇(PIPs)是CD14+吞噬细胞识别的凋亡信号。用抗PI(3，4，5)P3抗体、AKT和PLCδPH结构域和CD14蛋白观察到早期和晚期凋亡细胞表面的PIP位于斑块和水泡中。凋亡细胞的吞噬作用可被表面PIP或吞噬细胞中的CD14基因敲除所阻断。我们进一步证实了外周PIP+胸腺细胞在体内照射后显著增加，并且外周PIP+细胞在CD14−/−小鼠组织中的数量比WT小鼠更多，特别是在诱导细胞凋亡之后。我们的发现揭示了表面PIP是以前未知的细胞死亡信号，可以被CD14+吞噬细胞识别。
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.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
29.7
作者：
Brubaker SW;Bonham KS;Zanoni I;Kagan JC
通讯作者：
Kagan JC
影响因子：
12.4
作者：
Baek, J. O.;Roh, J. Y.;Jung, Y.
通讯作者：
Jung, Y.
影响因子：
29.4
作者：
Jensen, JN;Cameron, E;Jensen, J
通讯作者：
Jensen, J
影响因子：
14.8
作者：
Jiang, Lanzhou;Tixeira, Rochelle;Poon, Ivan K. H.
通讯作者：
Poon, Ivan K. H.