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April 4, 2017
An overlooked role for lungs in blood formation
At a Glance
- A study in mice provided direct evidence that the lung is a major site for production of platelets, a type of blood cell.
- The findings suggest new directions for developing treatments for people who have low levels of platelets.
All blood cells come from blood stem cells (progenitor cells). When blood cells become old or damaged and die, progenitor cells produce new blood cells to take their place. Although some blood progenitor cells are in the blood, most reside in the bone marrow.
Blood progenitor cells produce red blood cells, white blood cells, and platelets. The function of platelets is to help form blood clots to slow or stop bleeding. When the body doesn’t make enough platelets, it increases the risk of bruising and bleeding. Thrombocytopenia is a disorder caused by a very low platelet level. Severe cases can be treated with blood transfusions or medicine.
Researchers believed that the bone marrow was the major site of platelet production. But studies have found that blood leaving the lungs has more platelets and fewer progenitor cells than blood entering the lungs. To investigate whether platelet formation might be occurring in the lung, a research team led by Dr. Mark R. Looney of the University of California, San Francisco, used an imaging technology known as intravital microscopy. This technique enables scientists to observe cells moving in real time inside living mice. The work was funded in part by NIH’s National Heart, Lung, and Blood Institute (NHLBI). Results were published online on March 22, 2017, in Nature.
The researchers labeled the mouse model with fluorescent markers so that platelets and their progenitor cells would appear green against the red color of blood vessels and other cells. They made video recordings focusing on progenitor cells called megakaryocytes in the blood vessels of the lungs.
The team witnessed platelets bud from the megakaryocytes and flow away through the bloodstream. From the video footage, they were able to count the number of platelets formed per hour. They estimated that about half of total platelet production occurs in the lungs.
By performing a series of lung transplants between mice with certain deficiencies, the team discovered that blood cell progenitors were able to migrate out of the lung and into the bone marrow, where they could completely restore production of platelets and other blood cells.
“To our knowledge this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia,” Looney says.
“It has been known for decades that the lung can be a site of platelet production, but this study amplifies this idea by demonstrating that the murine [mouse] lung is a major participant in the process,” explains Dr. Traci Heath Mondoro, chief of NHLBI’s Translational Blood Science and Resources Branch. “Dr. Looney and his team have disrupted some traditional ideas about the pulmonary [the lung’s] role in platelet-related hematopoiesis [new blood cell production], paving the way for further scientific exploration of this integrated biology.”
—by Geri Piazza
References: The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Lefrançais E, Ortiz-Muñoz G, Caudrillier A, Mallavia B, Liu F, Sayah DM, Thornton EE, Headley MB, David T, Coughlin SR, Krummel MF, Leavitt AD, Passegué E, Looney MR. Nature. 2017 Mar 22. doi: 10.1038/nature21706. [Epub ahead of print] PMID: 28329764.
Funding: NIH’s National Heart, Lung, and Blood Institute (NHLBI), UCSF Nina Ireland Program in Lung Health, and UCSF Program for Breakthrough Biomedical Research.