Nobody could really accuse the lungs of not pulling their biological weight in mammals, but on top of their unarguable talent for oxygenating blood, it appears they also play a vital role in creating the red stuff in the first place.
That’s the conclusion of researchers from the University of California, who have discovered that mouse lungs produce over 10 million platelets per hour – the majority in their mousey circulations. While we knew that lungs can produce platelets, nobody really realised the scale that this study shows – until now, we’d assumed that it was bone marrow taking care of the lion’s share of things.
That doesn’t automatically follow that it’s the same in humans, but it would be a surprise if that wasn’t the case. As one of the researchers, professor Mark Looney explained: “What we’ve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.
“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.”
How had this crucial piece of information about lung function remained hidden for so long? Well, the discovery was made using relatively new technology based on two-photon intravital imaging. In short, green fluorescent protein (GFP) was inserted into the mouse genome, meaning that the platelets would emit a green light as they worked their way around the body. Using this method, the researchers were able to see where the megakaryocytes (the cell responsible for platelet generation) were concentrated.
They dug deeper and discovered that around one million megakaryocyte progenitor cells and blood stem cells were just outside the tissue of each mouse lung. While megakaryocytes were previously associated with bone marrow, it does appear that belief wasn’t completely off – they start life in the bone marrow, before transferring to the lungs where they begin their platelet production.
“It’s fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets,” said Guadalupe Ortiz-Muñoz, another member of the team. “It’s possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signalling we don’t yet know about.”
Interesting as this is, what does it actually mean for medicine? Well, the researchers were curious to know whether this discovery could help with disorders such as lung inflammation. To that end, they transplanted lungs with highlighted megakaryocyte progenitor cells into mice with low platelet counts. The result was a burst of platelet creation that pushed numbers up to normal levels for several months. A promising start.
The researchers then transplanted healthy lungs with highlighted cells into mice with bone marrow without normal blood stem cells. Amazingly, the scientists found that cells from the lungs traveled to the damaged bone marrow and worked over time – not only producing platelets, but also neutrophils, B Cells and T Cells. That suggests that the lungs have been hiding a whole bunch of blood progenitor cells and stem cells.
“We’re seeing more and more that the stem cells that produce the blood don’t just live in one place but travel around through the blood stream,” explained Looney. “Perhaps ‘studying abroad’ in different organs is a normal part of stem cell education.”
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