A few years ago, Andrew Chow, a Mount Sinai M.D./Ph.D. student in the laboratories of Drs. Frenette, and Miriam Merad, M.D., Ph.D., professor of oncological sciences and immunology at Mount Sinai found that bone marrow macrophages express a cell surface molecule called sialoadhesin, or CD169 a target that could be used for selectively eliminating macrophages from bone marrow. Doing so would help pinpoint the role of macrophages in erythroblastic islands in vivo.
That's what Drs. Frenette and Merad did in the current study involving mice. They found that selectively eliminating CD169-positive macrophages in mice reduces the number of bone marrow erythroblasts evidence that these macrophages are indeed vital for the survival of erythroblasts, which develop into RBCs.
"What was surprising is that we couldn't see any significant anemia afterward," said Dr. Frenette. The researchers then analyzed the lifespan of the red blood cells and found that they were circulating for a longer time than usual.
"After we depleted the macrophages in the bone marrow, we discovered that we had also depleted CD169-positive macrophages present in the spleen and liver. It turns out that the macrophages in these two organs are quite important in removing old red blood cells from the peripheral circulation. Taken together, the findings show that these macrophages have a dual role, both producing and clearing red blood cells," he said.
The researchers also examined the role of macrophages in polycythemia vera, a genetic disease in which the bone marrow produces too many RBCs, typically leading to breathing difficulties, dizziness, excessive blood clotting and other symptoms. Using a mouse model of polycythemia vera, they found that depleting CD169-positive macrophages in bon
|Contact: Kim Newman|
Albert Einstein College of Medicine