White blood cells found to play key role in controlling red blood cell levels

March 17, 2013

Researchers at Albert Einstein College of Medicine of Yeshiva University 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 the body's red blood cells (RBCs). The findings could lead to novel therapies for diseases or conditions in which the red blood cell production is thrown out of balance. The study, conducted in mice, is published today in the online edition of the journal Nature Medicine.

"Our findings offer intriguing new insights into how the body maintains a healthy balance of ," said study leader Paul Frenette, M.D., professor of medicine and of cell biology and director of the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research at Einstein. "We've shown that in the and the spleen nurture the production of new red 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 RBC counts, such as , polycythemia vera, and acute blood loss, plus aid recovery from chemotherapy and ." Einstein has filed a joint with Mount Sinai related to this research, which is currently available for licensing and further commercialization.

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, 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 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 bone marrow normalizes the RBC count. "This points to a new way to control polycythemia vera," said Dr. Frenette. "Right now, the standard of care is phlebotomy [periodic blood removal], which is cumbersome."

Explore further: A new way to boost red blood cell numbers

More information: The title of the paper is "CD169+ macrophages provide a niche promoting erythropoiesis under homeostasis and stress."

Related Stories

A new way to boost red blood cell numbers

January 10, 2008

A common treatment for anemia — a deficiency in red blood cells (rbcs) caused by their insufficient production, excessive destruction, or excessive loss — is administration of recombinant erythropoietin (Epo), a hormone ...

Researchers discover origin of immune cells in the brain

October 22, 2010

Mount Sinai researchers have discovered that microglia, the immune cells that reside in the brain, have a unique origin and are formed shortly after conception. It was previously thought that microglia originated at the ...

Recommended for you

Basic research fuels advanced discovery

August 26, 2016

Clinical trials and translational medicine have certainly given people hope and rapid pathways to cures for some of mankind's most troublesome diseases, but now is not the time to overlook the power of basic research, says ...

New avenue for understanding cause of common diseases

August 25, 2016

A ground-breaking Auckland study could lead to discoveries about many common diseases such as diabetes, cancer and dementia. The new finding could also illuminate the broader role of the enigmatic mitochondria in human development.

New method creates endless supply of kidney precursor cells

August 25, 2016

Salk Institute scientists have discovered the holy grail of endless youthfulness—at least when it comes to one type of human kidney precursor cell. Previous attempts to maintain cultures of the so-called nephron progenitor ...

Strict diet combats rare progeria aging disorders

August 25, 2016

Mice with a severe aging disease live three times longer if they eat thirty percent less. Moreover, they age much healthier than mice that eat as much as they want. These are findings of a joint study being published today ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

baudrunner
not rated yet Mar 17, 2013
Gee. We appear to have just stumbled upon the cause of auto-immune diseases. Overzealous white blood cells.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.