An unexpected result in a lab experiment could be a big step forward in the battle against anemia. The serendipitous discovery of a new way to trigger red blood cell production also reveals a surprising role for dendritic cells, a type of immune cell that was not thought to be involved in red blood cell production.
The team that did the work, led by Thomas J. Braciale, a professor of pathology and microbiology at the University of Virginia School of Medicine in Charlottesville, describes the discovery in The Journal of Clinical Investigation.
The discovery came about during a routine lab experiment where the team was investigating the role of dendritic cells in the lungs.
Anemia is a condition where the number of red blood cells – or their ability to carry oxygen – is insufficient for what the body needs. How much oxygen the body needs varies by age, gender, altitude, smoking and pregnancy status.
Iron deficiency is the most common cause of anemia. The condition can also arise as a result of chronic inflammation, parasite infections, inherited disorders and nutritional deficiencies in folate, vitamin B12 and vitamin A.
Severe anemia is linked to fatigue, weakness, dizziness and drowsiness. Pregnant women and children are particularly vulnerable. The World Health Organization (WHO) global estimate for 2011 suggests anemia affects around 800 million children and women.
Anemia can also affect people with diabetes and people with kidney disease or cancer. Chronic anemia is particularly prevalent in older adults.
Dendritic cells are known for their role in the immune system. They act as messengers that trigger the appropriate immune response to an incoming pathogen.
- Estimates suggest around one third of the world’s population is anemic
- About half of cases of anemia are caused by iron deficiency
- The burden of anemia is highest in sub-Saharan Africa, with South Asia also heavily affected.
But the researchers, who were running a test of the flu virus in mice, discovered an unexpected effect that led them to discover dendritic cells also have a completely different, and previously unknown, role.
They saw the effect when they injected the mice with the flu virus and an antibody that blocked a certain molecule expressed by dendritic cells.
The first thing that happened was the mice’s spleen become huge. This totally unexpected result baffled the researchers, so they ran the test again, and the same thing happened. Prof. Braciale takes up the story:
“We did it again and I didn’t believe it, and we did it again and I didn’t believe it. I asked whether you needed to flu infect the mice when you injected this antibody. So the postdoc [a lab member] did the experiment, and he just injected the antibody without flu injecting the mice. Giant spleens. After much consultation, after talking with my colleagues in Pathology, we decided we were inducing stress erythropoiesis.”
“Stress erythropoiesis” is where the body make more red blood cells in response to injury or some other stress. The team realized they had discovered a way to flip on a switch that triggers stress erythropoiesis – for example, use the antibody to get dendritic cells to trigger red blood cell production.
Prof. Braciale says it appears that the process of regulating stress in the body involves dendritic cells. Stress can arise from a number of sources – it can be infection, inflammation; it can be anemia, it can be hemorrhage.
Looking at infection and inflammation as stresses, it makes sense that dendritic cells have this extra role, although this study is the first evidence, it seems, that these cells are involved in producing red blood cells.
The team sees exciting potential in the method. For example, doctors could turn on red blood cell production when necessary.
Other possibilities include increasing red blood cells in soldiers on the battlefield waiting for blood transfusions and in people whose religious beliefs forbid them to have blood transfusions.
Although there is a lot of work to do before a treatment that triggers dendritic cells to make red blood cells is ready for use in humans, Prof. Braciale is optimistic, because, as he explains:
“We know that the same things can be done in humans in the following sense. There are mice called humanized mice. These are mice that are engineered so they have a human blood system. And if you inject these mice with this antibody, they’ll make red blood cells.”
Earlier this year, Medical News Today reported that lab-made blood is to enter human trials in 2 years. The intention is not to replace human donation but to offer specialist treatment for people with complex blood types for whom it is difficult to find matching donors.