Photo Credit: splice-bio.com

In your biology class, you may have learned that lungs help us breathe while bone marrow, found in flat bones such as the hip bone, produces red and white blood cells through a process called hematopoiesis. Now, University of California, San Francisco (UCSF) researchers have discovered that in addition to being a crucial part of our respiratory system, lungs also play a major role in the production and storage of blood cells.

Like many medical breakthroughs, the scientists stumbled upon this discovery by accident. The team, led by Professor Mark R. Looney, was trying to observe how platelets (cells that form clots to stop bleeding) circulating in the lungs interact with the immune system in mice. To trace the cells’ path, the rodents had been genetically modified so that the platelets appeared a glowing green.

To the scientists' astonishment, the lungs were filled with megakaryocytes — the cells responsible for producing platelets. Though experts have always known of the existence of these cells inside the lungs, they had believed the numbers to be tiny. Emma Lefrançais, who co-wrote the study, says, "When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up."

Visualization of resident megakaryocytes in the lungs. Image credit: Emma Lefrançais et al, doi: 10.1038/nature21706.

Further examination revealed that the megakaryocytes in the lungs were producing over 10 million platelets, or more than half the total platelets, produced by a mouse, every hour. The researchers also noticed the large population (1 million per mouse lung) of blood stem cells (which produce red blood cells) as well as megakaryocyte progenitor cells (which generate megakaryocyte cells) on the periphery of the lungs. Looney says, “To our knowledge, this is the first description of blood progenitors resident in the lung.”

To investigate the significance, the scientists conducted three studies. First, they transplanted lungs from normal mice into the genetically engineered ones to see how the blood stem cells move throughout the body. By following the fluorescent cells, they discovered that megakaryocytes originate in the bone marrow but migrate to the lungs to produce platelets.

To test the practical applications of this discovery and see if it would be useful in the treatment of disorders like lung inflammation, Looney’s team injected the fluorescent megakaryocyte progenitor cells into mice with low platelet counts. To their delight, the transplanted cells got to work immediately, restoring the platelet count to normal levels within a short time. What was even more encouraging is that the effect lasted for several months.

The role played by lungs in producing platelets (Image Credit: Emma Lefrançais et al, doi: 10.1038/nature21706)

Finally, the researchers transplanted healthy lungs in which all the cells had been fluorescently tagged into mice whose bone marrow was not producing blood cells or platelets. The researchers found that the glowing green megakaryocyte progenitor cells instantly migrated from the lungs to the bone marrow, where they helped to produce platelets and other critical blood components, like neutrophils, B cells, and T cells.

While the scientists, who published their findings in the journal Nature on March 22, 2017, still need to test if human lungs are as effective, the findings are being hailed as a major breakthrough. Traci Mondoro from the US National Heart, Lung, and Blood Institute, says, "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."

Resources: newatlas.com, UCSF.edu