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UNC scientists identify sticky protein in sickle cell red blood cells

CHAPEL HILL -- New research from the University of North Carolina at Chapel Hill reveals why red blood cells from people with sickle cell disease are stickier than healthy red cells, pointing the way to potential new treatments for sickle cell disease. The study shows that a protein found on the surface of immature red blood cells, or reticulocytes, is responsible for those cells' adhesion to blood vessel walls.

Reticulocytes are found at considerably higher levels in the blood of sickle cell patients than healthy patients, and so the likelihood of sticky patches or blockages forming on a blood vessel wall is greatly increased. The blockages lead to problems including strokes, pneumonia, recurring infections and painful episodes known as crises that often require hospitalization.

The new findings appear in the Oct. 8 issue of the Journal of Biological Chemistry.

The work of Dr. Julia Brittain provides new clues to better controlling stickiness of sickle red blood cells, said Dr. Leslie Parise, professor and vice chair of pharmacology at UNC's School of Medicine. Brittain is a postdoctoral fellow in Parise's laboratory.

"It was previously thought that sickle red blood cells lodged in blood vessels because they're sickle-shaped, more rigid and just became physically stuck," said Brittain, the study's co-author. "But while the physical lodging is a component, an equally important component is that sickle red blood cells are simply stickier."

Brittain and her co-authors showed that the cell-surface protein Alpha-4Beta-1 is activated by another cell-surface protein, CD47, and that Alpha-4Beta-1 was responsible for sickle red blood cell adhesion to a blood vessel wall protein called thrombospondin.

CD47 binds to and is activated by soluble, blood-borne thrombospondin, which is found elevated in sickle cell patients and which initiates an atypical signaling cascade inside the red blood cells. This aberrant
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Contact: L.H. Lang
llang@med.unc.edu
919-843-9687
University of North Carolina School of Medicine
12-Oct-2004


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