UNC scientists identify sticky protein in sickle cell red blood cells
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 UNCs School of Medicine. Brittain is a postdoctoral fellow in Parises laboratory. "It was previously thought that sickle red blood cells lodged in blood vessels because theyre sickle-shaped, more rigid and just became physically stuck," said Brittain, the studys 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 signaling ultimately culminates in the activation of Alpha-4Beta-1 and an increase in red blood cells sticking to the blood vessel wall, said Brittain.
"Even though sickle cell patients are particularly vulnerable to blocked blood vessels, the signaling mechanisms identified in sickle reticulocytes seem to be present in reticulocytes found in other anemic patients as well," said Brittain. "Our current thinking is that these results may benefit patients suffering from a number of anemias and not just sickle cell disease" The UNC study also identified where Alpha-4Beta-1 binds to thrombospondin. "This knowledge opens the door to possible therapies. Inhibitors of the class of proteins to which Alpha-4Beta-1 belongs, the integrins, are being tested for use in diseases such as Crohns disease, and these inhibitors are now attractive and rational therapies for sickle cell disease," said Parise.
L.H. Lang | EurekAlert!
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.
For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...
What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.
To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...
A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes
The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....
Larsen C Ice Shelf rift finally breaks through
A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...
Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision
Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...