Emma Lefrançais 1 , Guadalupe Ortiz-Muñoz 1 , Axelle Caudrillier 1 , Beñat Mallavia 1 , Fengchun Liu 1 , David M. Sayah 2 , Emily E. Thornton 3 , Mark B. Headley 3 , Tovo David 4 , Shaun R. Coughlin 4 , Matthew F. Krummel 3 , Andrew D. Leavitt 1 , Emmanuelle Passegué 1 , Mark R. Looney 1 , 5
22 March 2017
Platelets are critical for hemostasis, thrombosis, and inflammatory responses 1, 2 , yet the events leading to mature platelet production remain incompletely understood 3 . The bone marrow (BM) is proposed to be a major site of platelet production although indirect evidence points towards a potential pulmonary contribution to platelet biogenesis 4- 7 . By directly imaging the lung microcirculation in mice 8 , we discovered that a large number of megakaryocytes (MKs) circulate through the lungs where they dynamically release platelets. MKs releasing platelets in the lung are of extrapulmonary origin, such as the BM, where we observed large MKs migrating out of the BM space. The lung contribution to platelet biogenesis is substantial with approximately 50% of total platelet production or 10 million platelets per hour. Furthermore, we identified populations of mature and immature MKs along with hematopoietic progenitors that reside in the extravascular spaces of the lung. Under conditions of thrombocytopenia and relative stem cell deficiency in the BM 9 , these progenitors can migrate out of the lung, repopulate the BM, completely reconstitute blood platelet counts, and contribute to multiple hematopoietic lineages. These results position the lung as a primary site of terminal platelet production and an organ with considerable hematopoietic potential.