The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors.
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.
Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.
Emma
E
Lefrançais
Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.
Guadalupe
G
Ortiz-Muñoz
Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.
Axelle
A
Caudrillier
Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.
Beñat
B
Mallavia
Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.
Fengchun
F
Liu
Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, California 90095, USA.
David M
DM
Sayah
Department of Pathology, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.
Emily E
EE
Thornton
Department of Pathology, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.
Mark B
MB
Headley
Cardiovascular Research Institute, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.
Tovo
T
David
Cardiovascular Research Institute, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.
Shaun R
SR
Coughlin
Department of Pathology, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.
Matthew F
MF
Krummel
Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.
Andrew D
AD
Leavitt
Department of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.
Emmanuelle
E
Passegué
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.
Mark R
MR
Looney
D000818:Animals; D001792:Blood Platelets / Q000166:cytology*; D001853:Bone Marrow; D019070:Cell Lineage; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008168:Lung / Q000033:anatomy & histology / Q000098:blood supply* / Q000166:cytology*; D008297:Male; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D008833:Microcirculation; D010976:Platelet Count; D013921:Thrombocytopenia / Q000473:pathology