Red blood cell production in the bone marrow is a precarious process. Too few RBCs and you can become anemic; too many and you could be suffering from polycythemia vera, a rare, so-called ‘myeloproliferative’ genetic disorder marked by an abnormally high RBC count. Now, researchers have identified a surprising player in the regulation of RBC production under these disease conditions. Reporting online today in Nature Medicine, two independent teams describe the pivotal role of macrophages—amoeba-like white blood cells responsible for digesting harmful foreign microbes and removing old or dying cells—for generating RBCs in both anemic and over-proliferative conditions.
In one study, geneticist Stefano Rivella and his colleagues at the Weill Cornell Medical College in New York administered a drug that selectively kills macrophages in a mouse model of polycythemia vera. In these mice, RBCs are generated at almost twice the normal amount, leading to viscous blood, enlarged organs and increased risk for strokes and heart disease. The drug, called clodronate, appeared to cure these symptoms, however, drastically lowering macrophage population and bringing RBC counts back to normal levels compared with a control group of animals treated with saline.
These findings were independently confirmed by Paul Frenette, a stem cell biologist at the Albert Einstein College of Medicine, also in New York. His team used a genetically modified mouse in which macrophages expressed a gene that made them vulnerable to a toxin and arrived at similar conclusions. “When we depleted macrophages in this disease, we actually corrected the disease,” Frenette says. “Maybe this could be a new therapy for this type of disease, which is unexpected.”
