It has been widely believed that the bone marrow is the only hematopoietic organ in the human body, however, the top journal Nature has previously published important research findings by Professor Mark R. Looney’s team at the University of California, San Francisco (UCSF), who have demonstrated for the first time that the lung is a hematopoietic organ and that more than half of the platelets in animals come from the lung; more importantly, they have also found for the first time that the lung stores More importantly, they also discovered for the first time that the lungs store a variety of hematopoietic progenitor cells that can be used to restore the hematopoietic capacity of damaged bone marrow.
”There is no doubt that this important discovery proves that the lung is a very complex organ, not just a respiratory organ, but a key organ in the formation of important components of blood,” Professor Looney told Nicholas Weiler of the UCSF News Division. mice strongly suggest that the lungs also have a very important role in human blood formation.” For the millions of patients with blood disorders and those who need to receive lung transplants, this new discovery has the potential to have a huge and far-reaching impact on the treatment of their disease.
Professor Looney, an expert in the field of innate immunology of the lung, invented the “two-photon in vivo imaging technique” with fellow pathologist Professor Matthew F Krummel in 2011 to observe immune surveillance activity in the lungs of mice, a method that allows This imaging method allows researchers to perform very subtle observation tasks, allowing them to see the behavior of individual cells within tiny blood vessels in the lungs of living mice.
In a routine study, Professor Looney’s team was using two-photon live imaging to observe the interaction between platelets in the blood and the immune system in the lungs, and unexpectedly saw large numbers of platelet-producing megakaryocytes and various hematopoietic progenitor cells in the pulmonary vasculature (hematopoietic progenitor cells are differentiated from hematopoietic stem cells, which, in contrast to the all-powerful hematopoietic stem cells, can only proliferate to one or a few (In contrast to all-powerful hematopoietic stem cells, hematopoietic progenitor cells can only proliferate and differentiate to one or a few blood cell lineages. .
Platelets were first discovered in 1882. That year, an Italian doctor named J.B. Bizozzero (1846-1901; he was also the discoverer of Helicobacter pylori) discovered that what had long been considered a nonfunctional cellular fragment in the blood actually played an important role in the hemostasis process after vascular injury, and platelets got their name. Scientists have since discovered that the main functions of platelets are to clot and stop bleeding, repair broken blood vessels, and participate in the inflammatory response, but we still know very little about how they are actually produced.
Prior to this study, it was generally accepted that megakaryocytes were found primarily in the bone marrow, where they were responsible for the production of platelets. Although megakaryocytes had been observed in the lungs before and a strange phenomenon was observed: after the blood passed through the lungs, there were more platelets and fewer platelet-producing megakaryocytes; but it was not exactly known what was happening inside the lungs. So some people speculated that megakaryocytes were producing platelets in the lungs. But there was no direct evidence, and the question was left open for years.
When Professor Looney’s team used two-photon live imaging to see megakaryocyte activity in real time, Professor Looney thought an opportunity had presented itself. “When we saw the large number of megakaryocytes living in the lungs, we felt we had to see what they were doing in there,” Dr. Emma Lefrancais, the study’s first author, told Weiler.
So they built a model mouse in which megakaryocytes emit green fluorescence and then stared at the lungs of the mouse with a two-photon live imaging system to record the megakaryocytes’ every move. Soon, they made a startling discovery: megakaryocytes were producing platelets in the mice’s lungs, and they were producing more than 10 million per hour. This meant that more than half of the platelets in the mice came from the lungs and that the main organ producing platelets was not the bone marrow! The fog that had been hanging over the scientists’ minds was finally lifted. Finally, Professor Looney proved through lung transplantation experiments that the megakaryocytes inside the lungs were swimming from the bone marrow.
”It’s so interesting that megakaryocytes are crossing all the way from the bone marrow to the lungs to produce platelets,” Guadalupe ortiz-Munoz, the paper’s co-first author, told Weiler, “It’s possible that for megakaryocytes, the blood vessels inside the lungs are more narrower and the pressure generated is more favorable for them to produce platelets; it’s also possible that the lungs are releasing a signaling molecule that is more favorable for megakaryocytes to produce platelets.”
To verify the ability of the lung megakaryocytes to produce platelets, the researchers constructed a model mouse with low platelet levels and then transplanted them with a new lung that carried the green fluorescent protein-containing megakaryocytes. After the transplant was completed, the model mice’s platelet levels quickly rebounded with a green wave of platelets. This stable level lasted for several months, significantly longer than the lifespan of megakaryocytes and platelets. This was clearly a steady stream of megakaryocyte progenitors latent in the lungs differentiating into megakaryocytes that ensured stable platelet levels in the mice. The importance of the lungs to the stability of the blood components in animals is evident.
Since the hematopoietic progenitor cells in the lungs are so powerful, Professor Looney’s team wanted to see if the hematopoietic progenitor cells in the lungs could reverse the defect in model mice with defective bone marrow hematopoietic stem cells.
So they transplanted the model mice with lungs from healthy mice. Eventually, as expected, they found long-term hematopoietic stem cells, short-term hematopoietic stem cells, pluripotent progenitor cells 2 and pluripotent progenitor cells 3/4, as well as immune cells such as neutrophils, B cells and T cells in the bone marrow of the model mice. This means that the hematopoietic progenitor cells that reside inside the lungs can migrate to the bone marrow and restore its hematopoietic capacity when the bone marrow is damaged.
Professor Looney believes that this is the first time that academia has pointed to the existence of hematopoietic progenitor cells in the lungs. Dr. Guy A. Zimmerman, associate physician in charge of the Department of Internal Medicine at Utah State University School of Medicine, believes that this study changes our knowledge of blood cell formation, lung biology and disease, and organ metastasis.
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