| Autor: |
Lefrançais E; Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA., Ortiz-Muñoz G; Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA., Caudrillier A; Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA., Mallavia B; Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA., Liu F; Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA., Sayah DM; Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California 90095, USA., Thornton EE; Department of Pathology, University of California, San Francisco (UCSF), San Francisco, California 94143, USA., Headley MB; Department of Pathology, University of California, San Francisco (UCSF), San Francisco, California 94143, USA., David T; Cardiovascular Research Institute, University of California, San Francisco (UCSF), San Francisco, California 94143, USA., Coughlin SR; Cardiovascular Research Institute, University of California, San Francisco (UCSF), San Francisco, California 94143, USA., Krummel MF; Department of Pathology, University of California, San Francisco (UCSF), San Francisco, California 94143, USA., Leavitt AD; Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA., Passegué E; Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA., Looney MR; Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.; Department of Laboratory Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA. |
| Abstrakt: |
Platelets are critical for haemostasis, thrombosis, and inflammatory responses, but the events that lead to mature platelet production remain incompletely understood. 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. Here, by directly imaging the lung microcirculation in mice, 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, 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. |
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