Rescuing red cells to boost blood supply.

Rescuing red cells to boost blood supply

The human body normally takes about a week to replace a mature red blood cell, but after a major blood loss it can replenish the supply within only a few days. Physicians and researchers have long marveled at this ability, noting that much of the credit goes to a hormone called erythropoietin. When released by the kidneys after a blood loss, or when given as a drug, erythropoietin enhances red-cell production in the bone marrow. But just how it works has remained unclear.

Now, hematologists at Vanderbilt University Medical Center in Nashville provide evidence that erythropoietin works not by initiating new red-cell production but by preventing the "programmed death" of very young red cells in bone marrow.

Mark J. Koury and Maurice Bondurant used a unique system of cultured, immature red blood cells from mice, which mimics conditions in the bone marrow. Their research indicates that many of the billions of red-cell precursors produced in marrow every day are systematically destroyed before they develop into mature cells. At high enough levels, erythropoietin grants many of these precursor cells a stay of execution, enabling them to complete their marrow-based maturation and to take jobs as oxygen transporters in the circulatory system.

Their model suggests that red cells not granted an erythropoietin reprieve are especially susceptible to having their DNa digested by an enzymatic executioner or are impaired in their ability to repair damaged DNA. Since the erythropoietin protects cells already several days into their development, a surge of the hormone can boost the number of circulating cells more rapidly than would be possible if it exerted its influence at the very first stages of red-cell production.

An understanding of the mechanisms by which erythropoietin prevents DNA digestion or enhances DNA repair may lead to new therapies for anemias caused by vitamin deficiencies, toxic drugs or radiation therapies, Koury says. Details appear in the April 20 SCIENCE.