Challenging a long-held model about how blood is formed, a study led by UC San Francisco researchers has found that the lungs play a crucial role in the process, producing half of blood platelets and also storing blood-forming stem cells.

The study, performed in mice, also found that blood stem cells and progenitor cells travel freely between the lungs and bone marrow, long considered the primary source of blood production.

If found to occur in humans, this discovery about the lungs role in blood production could provide new approaches for treating blood diseases, pulmonologist Mark R. Looney, M.D., senior author of the study, said in a statement.

Moreover, the success of lung transplantation might be increased by better understanding this process. Immune reaction between donor blood cells in the lungs and the host could contribute to transplant rejection, the study stated.

The study was published Wednesday in the journal Nature. When placed online, the study can be found at j.mp/lungblood.

"This finding definitely suggests a more sophisticated view of the lungs -- that they're not just for respiration but also a key partner in formation of crucial aspects of the blood," Looney said. "What we've observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well."

"Dr. Looney and his team have disrupted some traditional ideas about the pulmonary role in platelet-related hematopoiesis, paving the way for further scientific exploration of this integrated biology," said Traci Mondoro, of the National Heart, Lung and Blood Institute, in the statement.

While it has been known for decades that platelets can be made in the lungs, the study indicates that lung production is a more important factor than previously thought, said Mondoro, project officer at the Translational Blood Science and Resources Branch of the NHLBI, a division of the National Institutes of Health.

Researchers studied the lungs of mice genetically engineered to make a green fluorescent protein in platelets and platelet-making cells called megakaryocytes. They found a larger than expected number of these cells.

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 study said. The contribution of the lungs to platelet biogenesis is substantial,accounting for approximately 50% of total platelet production or 10 million platelets per hour.

After discovering this process, the researchers looked for more signs of blood cells residing in the lungs. They found progenitor cells that turn into megakaryocytes, along with blood-forming, or hematopoietic, stem cells. a total of 1 million per mouse lung.

These cells constitute a reservoir that can replenish the bone marrow, the study said.

Under conditions of thrombocytopenia (platelet deficiency) 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 hematopoietic lineages, the study stated. These results identify the lungs as a primary site of terminal platelet production and an organ with considerable hematopoietic potential.

The studys co-first authors are Emma Lefranais and Guadalupe Ortiz-Muoz, both of UCSF. It was supported by the UCSF Nina Ireland Program in Lung Health; the UCSF Program for Breakthrough Biomedical Research, and the National Heart, Lung, and Blood Institute.

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