Sickle cell adhesion mechanism

The structural rigidity and irregular shape of erythrocytes in patients with sickle cell disease were considered to be the cause behind acute vaso-occlusive crises in these individuals. But, in June 15 Journal of Clinical Investigation, Julia Brittain and colleagues from the University of North Carolina at Chapel Hill, propose a new mechanism. They suggest that soluble thrombospondin can induce adhesion even in normal shaped sickle red blood cells via integrin-associated protein (IAP) signal transduction.

Brittain et al. used a system that mimics blood flow and shear conditions inside blood vessels. With this they demonstrated that occupancy of IAP on erythrocytes from patients with sickle cell disease induced adhesion of these cells to immobilized thrombospondin. In addition they showed that this mechanism occurs via the activation of a shear stress–dependent, G protein–mediated signal transduction pathway requiring a red cell tyrosine kinase (J Clin Invest 2001, 107:1555-1562).

These results suggest thrombospondin and ...