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On March 22, the prestigious journal *Nature* published a groundbreaking study (1) by Professor Mark R. Looney's team at the University of California, San Francisco (UCSF). For the first time, they confirmed that the lungs are a hematopoietic organ, with more than half of the platelets in animals originating from the lungs. Even more significantly, they discovered that the lungs store various hematopoietic progenitor cells, which can be used to restore the blood-forming capacity of damaged bone marrow.
"Without a doubt, this important discovery proves that the lungs are an incredibly complex organ—not just for respiration, but also as a key site for producing critical components of blood," Professor Looney told Nicholas Weiler of UCSF News. "What we observed in mice strongly suggests that the lungs play a significant role in human blood formation as well." This finding could have profound implications for millions of patients with blood disorders and those in need of lung transplants.
Professor Looney is an expert in pulmonary innate immunology. In 2011, while studying immune surveillance activity in mouse lungs, he and UCSF pathology expert Professor Matthew F. Krummel developed "two-photon intravital microscopy" (2PIVM) (2). This imaging technique allows researchers to observe the behavior of individual cells within the tiny blood vessels of living mouse lungs with remarkable precision.
During routine research, Looney's team used 2PIVM to examine the interaction between platelets and the lung's immune system. Unexpectedly, they observed large numbers of platelet-producing megakaryocytes and various hematopoietic progenitor cells in the lung vasculature. (Hematopoietic progenitor cells, derived from hematopoietic stem cells, can only differentiate into one or a few blood cell lineages, unlike multipotent stem cells.)
Platelets were first discovered in 1882 by Italian physician J.B. Bizozzero (1846–1901, who also identified *Helicobacter pylori*). He found that what had long been dismissed as nonfunctional cellular debris in blood actually played a crucial role in clotting after vascular injury—leading to the naming of platelets. Later, scientists determined that platelets primarily function in coagulation, wound healing, and inflammation, but their exact origins remained poorly understood (3).
Before this study, it was widely believed that megakaryocytes resided mainly in the bone marrow, where they produced platelets. Although megakaryocytes had been observed in the lungs before (4), along with the puzzling phenomenon that blood platelet counts increased after passing through the lungs while megakaryocyte numbers decreased (5), the exact mechanism remained unclear. Some speculated that platelets were being produced in the lungs, but without direct evidence, the question lingered unresolved for years.
When Looney's team witnessed megakaryocyte activity in real time using 2PIVM, he knew they had a breakthrough opportunity. "When we saw so many megakaryocytes in the lungs, we realized we had to investigate what they were doing there," said lead author Dr. Emma Lefrancais in an interview with Weiler.Thus, they created a model mouse in which megakaryocytes emit green fluorescence, then used a two-photon in vivo imaging system to observe the mouse's lungs, recording every move of the megakaryocytes. Soon, they made a startling discovery: megakaryocytes were producing platelets in the mouse's lungs, with a production rate exceeding 10 million per hour. This meant that over half of the platelets in the mouse's body originated from the lungs, revealing that the primary organ for platelet production was not the bone marrow! The long-standing mystery that had puzzled scientists was finally dispelled. In the end, Professor Looney demonstrated through lung transplant experiments that the megakaryocytes in the lungs had migrated from the bone marrow.
"This is fascinating—megakaryocytes actually travel all the way from the bone marrow to the lungs to produce platelets," Guadalupe Ortiz-Munoz, co-first author of the paper, told Weiler. "It's possible that for megakaryocytes, the narrower blood vessels in the lungs create pressure more conducive to platelet production. Alternatively, the lungs might release a signaling molecule that enhances platelet production by megakaryocytes."
To verify the platelet-producing capacity of lung megakaryocytes, the researchers engineered a model mouse with low platelet levels and transplanted a new lung into it—one carrying megakaryocytes with green fluorescent protein. After the transplant, the mouse's platelet levels quickly rebounded, with a surge of green-fluorescent platelets. This stable level persisted for months, far exceeding the lifespan of megakaryocytes and platelets. This clearly indicated that megakaryocyte progenitor cells lurking in the lungs continuously differentiated into megakaryocytes, ensuring stable platelet levels in the mouse. The importance of the lungs in maintaining blood composition stability in animals became evident.
Given the remarkable potency of hematopoietic progenitor cells in the lungs, Professor Looney's team wanted to investigate whether these cells could reverse hematopoietic defects in model mice with dysfunctional bone marrow stem cells.
They transplanted healthy mouse lungs into the model mice. Ultimately, they successfully identified long-term hematopoietic stem cells, short-term hematopoietic stem cells, multipotent progenitor cells 2 and 3/4, as well as immune cells like neutrophils, B cells, and T cells in the bone marrow of the model mice. This indicated that hematopoietic progenitor cells residing in the lungs could migrate to the bone marrow when it was damaged, restoring its hematopoietic capacity.
Professor Looney believes this is the first time the scientific community has identified the presence of hematopoietic progenitor cells in the lungs. Dr. Guy A. Zimmerman, Associate Chief of the Division of Internal Medicine at the University of Utah School of Medicine, stated that this research transforms our understanding of blood cell formation, lung biology and disease, and organ transplantation.References:
[1] Lefrançais E, Ortiz-Muñoz G, Caudrillier A, Mallavia B, Liu F, et al. 2017. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature advance online publication.
[2] Looney MR, Thornton EE, Sen D, Lamm WJ, Glenny RW, Krummel MF. 2011. Stabilized imaging of immune surveillance in the mouse lung. Nat Meth 8:91-6.
[3] Machlus KR, Italiano JE. 2013. The incredible journey: From megakaryocyte development to platelet formation. The Journal of Cell Biology 201:785-96.
[4] Aschoff L. 1893. Uber capillare Embolie von riesenkernhaltigen Zellen. Arch Pathol Anat Phys 134:11-4.
[5] Howell WH, Donahue DD. 1937. THE PRODUCTION OF BLOOD PLATELETS IN THE LUNGS. The Journal of Experimental Medicine 65:177-203.
[6] http:/ / www. ucsf. edu/ news/ 201……- new- role- lungs- making- blood
Editor: Li Zhi
Source: http://www. soundofhope. org/ b5/ 2017/ 03/ 24/ n809316. html
Nature's Shocking Discovery: Lungs are A Blood-Producing Organ!
"Without a doubt, this important discovery proves that the lungs are an incredibly complex organ—not just for respiration, but also as a key site for producing critical components of blood," Professor Looney told Nicholas Weiler of UCSF News. "What we observed in mice strongly suggests that the lungs play a significant role in human blood formation as well." This finding could have profound implications for millions of patients with blood disorders and those in need of lung transplants.
Professor Looney is an expert in pulmonary innate immunology. In 2011, while studying immune surveillance activity in mouse lungs, he and UCSF pathology expert Professor Matthew F. Krummel developed "two-photon intravital microscopy" (2PIVM) (2). This imaging technique allows researchers to observe the behavior of individual cells within the tiny blood vessels of living mouse lungs with remarkable precision.
During routine research, Looney's team used 2PIVM to examine the interaction between platelets and the lung's immune system. Unexpectedly, they observed large numbers of platelet-producing megakaryocytes and various hematopoietic progenitor cells in the lung vasculature. (Hematopoietic progenitor cells, derived from hematopoietic stem cells, can only differentiate into one or a few blood cell lineages, unlike multipotent stem cells.)
Platelets were first discovered in 1882 by Italian physician J.B. Bizozzero (1846–1901, who also identified *Helicobacter pylori*). He found that what had long been dismissed as nonfunctional cellular debris in blood actually played a crucial role in clotting after vascular injury—leading to the naming of platelets. Later, scientists determined that platelets primarily function in coagulation, wound healing, and inflammation, but their exact origins remained poorly understood (3).
Before this study, it was widely believed that megakaryocytes resided mainly in the bone marrow, where they produced platelets. Although megakaryocytes had been observed in the lungs before (4), along with the puzzling phenomenon that blood platelet counts increased after passing through the lungs while megakaryocyte numbers decreased (5), the exact mechanism remained unclear. Some speculated that platelets were being produced in the lungs, but without direct evidence, the question lingered unresolved for years.
When Looney's team witnessed megakaryocyte activity in real time using 2PIVM, he knew they had a breakthrough opportunity. "When we saw so many megakaryocytes in the lungs, we realized we had to investigate what they were doing there," said lead author Dr. Emma Lefrancais in an interview with Weiler.Thus, they created a model mouse in which megakaryocytes emit green fluorescence, then used a two-photon in vivo imaging system to observe the mouse's lungs, recording every move of the megakaryocytes. Soon, they made a startling discovery: megakaryocytes were producing platelets in the mouse's lungs, with a production rate exceeding 10 million per hour. This meant that over half of the platelets in the mouse's body originated from the lungs, revealing that the primary organ for platelet production was not the bone marrow! The long-standing mystery that had puzzled scientists was finally dispelled. In the end, Professor Looney demonstrated through lung transplant experiments that the megakaryocytes in the lungs had migrated from the bone marrow.
"This is fascinating—megakaryocytes actually travel all the way from the bone marrow to the lungs to produce platelets," Guadalupe Ortiz-Munoz, co-first author of the paper, told Weiler. "It's possible that for megakaryocytes, the narrower blood vessels in the lungs create pressure more conducive to platelet production. Alternatively, the lungs might release a signaling molecule that enhances platelet production by megakaryocytes."
To verify the platelet-producing capacity of lung megakaryocytes, the researchers engineered a model mouse with low platelet levels and transplanted a new lung into it—one carrying megakaryocytes with green fluorescent protein. After the transplant, the mouse's platelet levels quickly rebounded, with a surge of green-fluorescent platelets. This stable level persisted for months, far exceeding the lifespan of megakaryocytes and platelets. This clearly indicated that megakaryocyte progenitor cells lurking in the lungs continuously differentiated into megakaryocytes, ensuring stable platelet levels in the mouse. The importance of the lungs in maintaining blood composition stability in animals became evident.
Given the remarkable potency of hematopoietic progenitor cells in the lungs, Professor Looney's team wanted to investigate whether these cells could reverse hematopoietic defects in model mice with dysfunctional bone marrow stem cells.
They transplanted healthy mouse lungs into the model mice. Ultimately, they successfully identified long-term hematopoietic stem cells, short-term hematopoietic stem cells, multipotent progenitor cells 2 and 3/4, as well as immune cells like neutrophils, B cells, and T cells in the bone marrow of the model mice. This indicated that hematopoietic progenitor cells residing in the lungs could migrate to the bone marrow when it was damaged, restoring its hematopoietic capacity.
Professor Looney believes this is the first time the scientific community has identified the presence of hematopoietic progenitor cells in the lungs. Dr. Guy A. Zimmerman, Associate Chief of the Division of Internal Medicine at the University of Utah School of Medicine, stated that this research transforms our understanding of blood cell formation, lung biology and disease, and organ transplantation.References:
[1] Lefrançais E, Ortiz-Muñoz G, Caudrillier A, Mallavia B, Liu F, et al. 2017. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature advance online publication.
[2] Looney MR, Thornton EE, Sen D, Lamm WJ, Glenny RW, Krummel MF. 2011. Stabilized imaging of immune surveillance in the mouse lung. Nat Meth 8:91-6.
[3] Machlus KR, Italiano JE. 2013. The incredible journey: From megakaryocyte development to platelet formation. The Journal of Cell Biology 201:785-96.
[4] Aschoff L. 1893. Uber capillare Embolie von riesenkernhaltigen Zellen. Arch Pathol Anat Phys 134:11-4.
[5] Howell WH, Donahue DD. 1937. THE PRODUCTION OF BLOOD PLATELETS IN THE LUNGS. The Journal of Experimental Medicine 65:177-203.
[6] http:/ / www. ucsf. edu/ news/ 201……- new- role- lungs- making- blood
Editor: Li Zhi
Source: http://www. soundofhope. org/ b5/ 2017/ 03/ 24/ n809316. html