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

Autor: Emily E. Thornton, Fengchun Liu, Mark B. Headley, Mark R. Looney, David M. Sayah, Guadalupe Ortiz-Muñoz, Emmanuelle Passegué, Tovo David, Matthew F. Krummel, Beñat Mallavia, Shaun R. Coughlin, Axelle Caudrillier, Andrew D. Leavitt, Emma Lefrançais
Přispěvatelé: Department of Medicine, Microbiology and Immunology (UCSF), University of California [San Francisco] (UCSF), University of California-University of California-Rosalind Russell Medical Research Center
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Blood Platelets
[SDV]Life Sciences [q-bio]
Elephants
Biology
[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
Article
Microcirculation
03 medical and health sciences
Mice
0302 clinical medicine
medicine
[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Animals
Platelet
Progenitor cell
ComputingMilieux_MISCELLANEOUS
Multidisciplinary
Lung
Hematopoietic Stem Cell Transplantation
[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
medicine.disease
Thrombosis
Hematopoiesis
Haematopoiesis
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Immunology
Bone marrow
Stem cell
Megakaryocytes
Zdroj: Nature
Nature, Nature Publishing Group, 2017, 544 (7648), pp.105-109. ⟨10.1038/nature21706⟩
ISSN: 0028-0836
1476-4679
Popis: 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.
Databáze: OpenAIRE
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