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

2017; Nature Portfolio; Volume: 544; Issue: 7648 Linguagem: Inglês

10.1038/nature21706

1476-4687

Emma Lefrançais, Guadalupe Ortiz-Muñoz, Axelle Caudrillier, Beñat Mallavia, Fengchun Liu, D. Sayah, Emily Thornton, Mark B. Headley, Tovo David, Shaun R. Coughlin, Matthew F. Krummel, Andrew D. Leavitt, Emmanuelle Passegué, Mark R. Looney,

Blood properties and coagulation

Direct imaging of the lung microcirculation in mice indicates that it is a major site of mature platelet production from megakaryocytes. Platelets, which are essential for generating clots to stop bleeding, are produced to a large extent in the bone marrow, but indirect evidence points to a pulmonary contribution to their genesis. Emma Lefrançais et al. imaged microcirculation in the lungs of mice and report that the lung serves as a reservoir for haematopoietic progenitors and platelet-releasing megakaryocytes that can be recruited to compensate for bone marrow deficiencies. They estimate that the lung is responsible for around 50% of total platelet production in mice, a finding that positions it as an organ of notable haematopoietic potential. Platelets are critical for haemostasis, thrombosis, and inflammatory responses1,2, but the events that lead to mature platelet production remain incompletely understood3. 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 biogenesis4,5,6,7. Here, by directly imaging the lung microcirculation in mice8, 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 marrow9, 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.