The sudden bouts of pain that can afflict people with sickle cell anemia may occur when blood vessel linings become sticky and cause deformed red cells to clump up. The finding, reported in tomorrow's New England Journal of Medicine, could lead to new methods for studying and treating sickle cell illnesses.
Researchers have long known that a single flawed gene causes sickle cell disease, in which red blood cells take on a sicklelike shape that inefficiently delivers oxygen. But they haven't been able to explain fully how this simple defect produces the disease's debilitating array of symptoms, from aching joints to sudden pain. One idea is that the deformed cells cling to endothelial cells that line blood vessels, promoting blockages that can temporarily starve other cells of oxygen.
To test that theory, Robert Hebbel, Anna Solovey, and colleagues at the University of Minnesota, Minneapolis, and the Fred Hutchinson Cancer Research Center in Seattle, Washington, collected blood samples from people with and without sickle cell anemia. They found that the blood of people suffering from sickle cell crises contained up to 10 times the number of loose endothelial cells as that of healthy people. Most importantly, the cells were "activated" in the sickle cell patients, producing adhesive molecules. But the researchers caution that they still need to show that this reaction occurs in the blood vessels themselves.
The study is the first to show that activated endothelial cells are linked to sickle cell crises, says Bertram Lubin, a researcher with Children's Hospital in Oakland, California. Eventually, he says, the findings could help scientists better understand the factors that trigger activation, leading to treatments that make the cells less adhesive. Such treatments could benefit millions: About 60% of Africans and 10% of African Americans carry the sickle cell gene, although a smaller fraction suffers from all the disease's symptoms.