Laboratory of Biochemistry & Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Laboratory of Biochemistry & Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.
Curr Opin Immunol. 2021 Feb;68:1-8. doi: 10.1016/j.coi.2020.07.007. Epub 2020 Aug 24.
Macrophages specifically engulf apoptotic cells but not healthy cells. Phosphatidylserine (PtdSer) is localized at the inner leaflet of plasma membranes as a result of the action of flippases (ATP11A and 11C). When cells undergo apoptosis, caspase 3 cleaves and inactivates the flippases, while simultaneously cleaving XKR8 to activate its phospholipid scramblase activity. PtdSer is thus swiftly and irreversibly exposed to the cell surface as an 'eat me' signal. Tissue resident macrophages recognize the apoptotic cells using a PtdSer-receptor TIM4 and engulf them with TAM tyrosine-kinase receptors, and integrins. The PtdSer 'eat me' signal appears to override 'don't eat me' signals in most cases.
巨噬细胞特异性吞噬凋亡细胞而不是健康细胞。由于翻转酶（ATP11A 和 11C）的作用，磷脂酰丝氨酸（PtdSer）位于质膜的内叶。当细胞发生凋亡时，半胱天冬酶 3 切割并失活翻转酶，同时切割 XKR8 以激活其磷脂 scramblase 活性。因此，PtdSer 迅速且不可逆地暴露在细胞表面作为“吃我”信号。组织驻留巨噬细胞使用 PtdSer 受体 TIM4 识别凋亡细胞，并通过 TAM 酪氨酸激酶受体和整合素吞噬它们。在大多数情况下，PtdSer“吃我”信号似乎会覆盖“不要吃我”信号。
