The research team then looked at diseases in which there are too many red blood cell factories. Polycythemia vera was one of the conditions examined. The researchers disabled macrophage functioning in mice with polycythemia vera and found that red blood cell production returned to normal.
In beta-thalassemia, the body increases the number of red blood cell factories to make up for the lack of viable blood cells -- a strategy that doesn't work. As a result, patients develop enlarged spleens and livers due to the overload of erythroblasts in those organs.
The researchers found in mouse models that if they suppress the function of macrophages, the number of blood cell factories revert back to normal levels. However, there was also an additional benefit discovered. One of the functions of macrophages is to put excess recycled iron into erythroblasts. Researchers report if you suppress that function, less iron goes into the red blood cells. "So you then make red blood cells that have less iron, and they are now closer in structure to what they should be," says Dr. Rivella.
In animal studies, the researchers saw that decoupling macrophages from the erythroblasts not only reduced the number of blood cell factories, but also improved anemia.
The discovery could be translated into an experimental therapy by finding the molecule that physically binds a macrophage to an erythroblast, and then targeting and inhibiting it. "We need macrophages for good health, but it may be possible to decouple the macrophages that contribute to blood disorders," Dr. Rivella says. "I estimate that up 30 to 40 percent of the beta-thalassemia population could benefit from this treatment strategy."
Dr. Rivella also made another connection. He says polycythemia vera "is sort of a tumor of the red cells, because you m
|Contact: Lauren Woods|
Weill Cornell Medical College