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The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors

机译：肺是血小板生物发生的场所，也是造血祖细胞的储存库

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摘要

Platelets are critical for haemostasis, thrombosis, and inflammatory responses(1,2), but the events that lead to mature platelet production remain incompletely understood(3). The bone marrow has been proposed to be a major site of platelet production, although there is indirect evidence that the lungs might also contribute to platelet biogenesis(4-7). Here, by directly imaging the lung microcirculation in mice(8), we show that a large number of megakaryocytes circulate through the lungs, where they dynamically release platelets. Megakaryocytes that release platelets in the lungs originate from extrapulmonary sites such as the bone marrow; we observed large megakaryocytes migrating out of the bone marrow space. The contribution of the lungs to platelet biogenesis is substantial, accounting for approximately 50% of total platelet production or 10 million platelets per hour. Furthermore, we identified populations of mature and immature megakaryocytes along with haematopoietic progenitors in the extravascular spaces of the lungs. Under conditions of thrombocytopenia and relative stem cell deficiency in the bone marrow(9), these progenitors can migrate out of the lungs, repopulate the bone marrow, completely reconstitute blood platelet counts, and contribute to multiple haematopoietic lineages. These results identify the lungs as a primary site of terminal platelet production and an organ with considerable haematopoietic potential.
机译：血小板对于止血，血栓形成和炎症反应至关重要（1,2），但是导致成熟血小板生成的事件仍未完全了解（3）。尽管有间接证据表明肺可能也促进了血小板的生物发生，但骨髓被认为是血小板产生的主要部位（4-7）。在这里，通过对小鼠的肺微循环进行直接成像（8），我们发现大量的巨核细胞在肺中循环，并在那里动态释放血小板。在肺部释放血小板的巨核细胞起源于肺外部位，例如骨髓。我们观察到大型巨核细胞移出骨髓腔。肺对血小板生物发生的贡献很大，约占血小板总产量的50％或每小时一千万个血小板。此外，我们确定了肺血管外空间中成熟和未成熟的巨核细胞以及造血祖细胞的种群。在血小板减少症和骨髓中相对干细胞缺乏的情况下（9），这些祖细胞可以移出肺部，重新填充骨髓，完全重建血小板计数，并促成多种造血谱系。这些结果确定了肺是终末血小板产生的主要部位，并且是具有相当大的造血潜能的器官。

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  • 来源
    《Nature》 |2017年第7648期|105-109|共5页
  • 作者

    Lefrancais Emma; Ortiz-Munoz Guadalupe; Caudrillier Axelle; Mallavia Benat; Liu Fengchun; Sayah David M.; Thornton Emily E.; Headley Mark B.; David Tovo; Coughlin Shaun R.; Krummel Matthew F.; Leavitt Andrew D.; Passegue Emmanuelle; Looney Mark R.;

  • 作者单位

    Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA;

    Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA;

    Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA|Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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