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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Constitutive exposure of phosphatidylserine on viable cells
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Constitutive exposure of phosphatidylserine on viable cells

机译：磷脂酰丝氨酸在活细胞上的组成性暴露

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摘要

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 trans-membrane segments, has the Ca-dependent phospholipid scram-blase 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 interleu-kin 3 and underwent apoptosis upon treatment with Fas ligand. The viable PS-exposing cells bound to peritoneal macrophages at 4 ℃, but not at 25 ℃. 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.
机译：吞噬细胞可以迅速识别并吞噬凋亡细胞，以防止有害物质从垂死的细胞中释放出来。暴露于凋亡细胞表面的磷脂酰丝氨酸（PS）是吞噬细胞的“进食”信号。跨膜蛋白16F（TMEM16F）是具有八个跨膜区段的膜蛋白，具有Ca依赖性磷脂稀疏酶活性。在这里，我们显示出，当淋巴瘤细胞用组成型活性形式的TMEM16F转化时，它们暴露的高水平PS与凋亡细胞上观察到的水平相当。暴露于PS的细胞在形态上正常并且正常生长。他们有效地应答白介素3，并在用Fas配体处理后发生凋亡。暴露于PS的活细胞在4℃而不是25℃时与腹膜巨噬细胞结合。因此，这些细胞没有被巨噬细胞吞噬。当注射凋亡细胞时。进入小鼠后，它们被脾脏中的CD11c〜+ CD8〜+树突状细胞（DC）吞噬，但是暴露于PS的活细胞未被这些DC吞噬。此外，当暴露于PS的淋巴瘤细胞经皮下移植时。在裸鼠体内，它们产生的肿瘤与不暴露PS的亲代淋巴瘤细胞一样有效。这些结果表明，仅PS暴露不足以被巨噬细胞识别为“吃我”信号。

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  • 作者

    Katsumori Segawa; Jun Suzuki; Shigekazu Nagata;

  • 作者单位

    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan;

    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan;

    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan,Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Kyoto 606-8501, Japan;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    pospholipid asymmetry; pagocytosis;

    机译：磷脂不对称吞噬作用;

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