Unexpected new lung function discovered: Making blood
Our bodies still hold plenty of secrets, and scientists have just uncovered a doozy: the lungs play a key role in producing blood. Until now, this task was ascribed solely to bone marrow, but studies on mice at the University of California San Francisco (UCSF) have found that, surprisingly, the majority of the body's platelets are produced in the lungs, as is a backup reservoir of blood stem cells that can step in when those in the bone marrow run dry.
Science has long believed that most of the cells that make up blood reside in bone marrow, where a process called haematopoiesis gives us the oxygen-carrying red blood cells, the white blood cells that fight off infection, and components like platelets, whose role is to form clots to stop bleeding. Megakaryocytes – the cells that produce platelets – have been spotted in lung tissue before, but were usually thought to live and work mainly in bone marrow.
The UCSF study discovered the new function while imaging the lungs of living mice to investigate how platelets circulating through the lungs were interacting with the immune system. The mice in question had been engineered so that their platelets glowed green, which highlighted an unexpectedly high number of megakaryocytes in the organs.
"When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up," says Emma Lefrançais, co-first author of the study.
On closer inspection, the team found that the megakaryocytes in the lungs were creating more than 10 million platelets an hour, constituting more than half of a mouse's total amount. That population appears to be fed by a group of megakaryocyte progenitor cells and blood stem cells that are living just outside the main lung vasculature. The team spotted these cells – numbering at around a million per lung – with video microscopy techniques.
"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," says Mark R. Looney, MD, senior author of the study. "What we've observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well."
While the lungs may appear to be doing much of the work, bone marrow is no slouch. In fact, the two seem to work together to make blood. To study how the blood stem cells might move back and forth between the lungs and bone marrow, the UCSF team transplanted lungs from normal mice into engineered animals with fluorescent megakaryocytes, and it wasn't long before the glowing cells began to appear in the vasculature of the "normal" lung. That indicates that although the megakaryocytes may appear in greater numbers in the lung, they're still born inside bones, before migrating.
"It's fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets," says Guadalupe Ortiz-Muñoz, co-first author of the study. "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 signaling we don't yet know about."
In the other direction, lungs from mice with fluorescent megakaryocyte progenitor cells were transplanted into mice with low platelet counts. The team noticed that the animal's platelet counts quickly returned to healthy levels after the production of a large burst of glowing platelets, suggesting that the low count had prompted the implanted megakaryocyte cells to compensate.
In the third and final transplant study, the team wanted to investigate how the megakaryocytes in the lungs might handle the load when those in the bone marrow weren't pulling their weight. To that end, the researchers implanted lungs that had cells tagged with fluorescence into mice engineered so that their bone marrow didn't contain blood stem cells. Glowing cells from the transplanted lungs soon showed up in the bone marrow, where they helped to produce not just platelets, but also other key blood cells like neutrophils, B cells and T 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," says Looney. "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. Perhaps 'studying abroad' in different organs is a normal part of stem cell education."
The findings should help inform new studies into treatments for diseases that affect platelet production, and provides a better understanding of the active role stem cells play in the body. Future research could apply the discovery to the human body, and look into how the lungs and bone marrow work together to produce blood.
The study was published in the journal Nature, and the platelet production can be seen in the video below.