Blood: Macrophages Control Red Blood Cells


Photo: Macrophage and red blood cell

Macrophages, or white blood cells, help control the level of red blood cells;

Researchers at Albert Einstein College of Medicine and the Icahn School of Medicine at Mount Sinai have found that macrophages – white blood cells that play a key role in the immune response – also help to both produce and eliminate red blood cells.

The findings could lead to novel therapies for diseases or conditions in which the red blood cell production is thrown out of balance. "Our findings offer intriguing new insights into how the body maintains a healthy balance of red blood cells," said medical doctor Paul Frenette, professor of medicine and of cell biology at Einstein.

"We have shown that macrophages in the bone marrow and the spleen nurture the production of new red blood cells at the same time that they clear aging red blood cells from the circulation. This understanding may ultimately help us to devise new therapies for conditions that lead to abnormal red blood cell (RBC) counts, such as hemolytic anemia, polycythemia vera, and acute blood loss, plus aid recovery from chemotherapy and bone marrow transplantation."

Previous studies, all done in the laboratory, had suggested that macrophages in the bone marrow act as nurse cells for erythroblasts, which are RBC precursors. But just how these "erythroblastic islands" (macrophages surrounded by erythroblasts) function in living animals was unclear.
A few years ago the team 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 is what the team 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 could not see any significant anemia afterward," said 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 bone marrow normalizes the RBC count. "This points to a new way to control polycythemia vera," said Frenette. "Right now, the standard of care is phlebotomy [periodic blood removal], which is cumbersome."; Source: Albert Einstein College of Medicine