Constitutive exposure of phosphatidylserine on viable cells
Constitutive exposure of phosphatidylserine on viable cells
复制标题
DOI：
10.1073/pnas.1114799108
复制
发表时间：
2011-11-29
影响因子：
11.1
通讯作者：
Nagata, Shigekazu
中科院分区：
文献类型：
--
作者：
Segawa, Katsumori;Suzuki, Jun;Nagata, Shigekazu
凋亡细胞被吞噬细胞迅速识别并吞噬，以防止死亡细胞释放有害物质。磷脂酰丝氨酸（PS）暴露在凋亡细胞的表面是一个建议的“吃我”的吞噬细胞的信号。跨膜蛋白16 F（Transmembrane protein 16 F，TMEM 16 F）是一种具有钙离子依赖性的磷脂酶活性的跨膜蛋白。在这里，我们表明，当淋巴瘤细胞转化与组成型活性形式的TMEM16 F，他们暴露了高水平的PS，这是与观察到的凋亡细胞。PS暴露的细胞形态正常，生长正常。他们有效地响应白细胞介素3和Fas配体处理后发生凋亡。暴露于PS的活细胞在4 ℃下与腹腔巨噬细胞结合，但在25 ℃下不结合。因此，这些细胞不被巨噬细胞吞噬。当将凋亡细胞静脉注射到小鼠体内时，它们被脾脏中的CD11c（+）CD8（+）树突状细胞（DCs）吞噬，但暴露于PS的活细胞不被这些DCs吞噬。此外，当PS暴露的淋巴瘤细胞s.c.在裸鼠体内，它们产生肿瘤的效率与没有暴露PS的亲本淋巴瘤细胞一样高。这些结果表明，单独的PS暴露不足以被巨噬细胞识别为“吃我”信号。
Apoptotic cells are quickly recognized and engulfed by phagocytes to prevent the release of noxious materials from dying cells. Phosphatidylserine (PS) exposed on the surface of apoptotic cells is a proposed "eat-me" signal for the phagocytes. Transmembrane protein 16F (TMEM16F), a membrane protein with eight transmembrane segments, has the Ca-dependent phospholipid scramblase activity. Here we show that when lymphoma cells were transformed with a constitutively active form of TMEM16F, they exposed a high level of PS that was comparable to that observed on apoptotic cells. The PS-exposing cells were morphologically normal and grew normally. They efficiently responded to interleukin 3 and underwent apoptosis upon treatment with Fas ligand. The viable PS-exposing cells bound to peritoneal macrophages at 4 degrees C, but not at 25 degrees C. Accordingly, these cells were not engulfed by macrophages. When apoptotic cells were injected i.v. into mice, they were phagocytosed by CD11c(+) CD8(+) dendritic cells (DCs) in the spleen, but the PS-exposing living cells were not phagocytosed by these DCs. Furthermore, when PS-exposing lymphoma cells were transplanted s.c. into nude mice, they generated tumors as efficiently as parental lymphoma cells that did not expose PS. These results indicated that PS exposure alone is not sufficient to be recognized by macrophages as an eat-me signal.