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In possible boon to sickle cell victims, basic scientists find reason cells stick

CHAPEL HILL - Despite recent advances in treating sickle cell disease, an inherited illness chiefly affecting black people in the United States, patients still suffer periodic painful episodes known as crises.

Those debilitating events result from misshapen red blood cells sticking to and clogging up blood vessels like twigs in a pipe and blocking oxygen supply to various tissues. Organ damage and shortened life spans often result.

Now, researchers at the University of North Carolina at Chapel Hill have discovered a protein on the surface of sickled red cells that causes them to stick to another protein that is part of blood vessel walls. Their work, so far confined to the test tube, offers new hope that treatments for sickle cell disease will improve, they say.

A report on the experiments, funded by the National Institutes of Health, appears in the April 1 issue of the journal Blood. Authors, all at the UNC School of Medicine, are Dr. Julia E. Brittain, postdoctoral fellow in pharmacology; medical student Kathryn J. Milnar; technician Christopher S. Anderson; Dr. Eugene P. Orringer, professor of medicine; and Dr. Leslie V. Parise, professor of pharmacology.

"We had previously found that sickle red blood cells in these patients are, in a sense, 'stickier' than normal red blood cells," Parise said. "In our new work, we have identified integrin-associated protein, or IAP, on sickled cells as a receptor for thrombospondin, a blood vessel wall protein. IAP now becomes a potential new therapeutic target for preventing the cells from adhering to the vessels."

The findings are possibly good news for sickle cell patients because the team may have identified the mechanism, or one of the mechanisms, that causes the painful crises, she said. Understanding what's involved in such an important process could be the key to controlling it.

Brittain said the team's experiments used a system that mimics blood flow and shear conditions inside blood vessel
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Contact: David Williamson
David_Williamson@unc.edu
919-962-8596
University of North Carolina at Chapel Hill
1-Apr-2001


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