Hydroxycarbamide decreases sickle reticulocyte adhesion to resting endothelium by inhibiting endothelial lutheran/ basal cell adhesion molecule (Lu/BCAM) through phosphodiesterase 4A activation

Abstract

Background: Hydroxycarbamide treatment may inhibit the proadhesive features of vascular endothelium in sickle cell disease. Results: Hydroxycarbamide treatment of endothelial cells inhibits the interaction between erythroid integrin 4 1 and endothelial Lu/BCAM. Conclusion: Hydroxycarbamide increases the expression of phosphodiesterase 4A, which decreases cAMP levels leading to less Lu/BCAM phosphorylation and less cell adhesion. Significance: This is the first example of a phosphodiesterase being regulated by hydroxycarbamide. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.