Band 3 peptides block the adherence of sickle cells to endothelial cells in vitro.

Malaria-parasitized erythrocytes have increased endothelial adherence due to exposure of previously buried intramembranous sites of band 3. Because sickle erythrocytes also show increased adhesiveness and because the membrane portion of band 3 is aggregated in both types of cells, we examined the role of band 3 in sickle cell adhesiveness. Synthetic peptides derived from the second and third exofacial, interhelical regions of band 3 completely inhibited the abnormal adherence of sickle cells to an endothelial monolayer in a static assay. This effect was observed independently of plasma factors, required micromolar levels of peptide, was sequence-specific, and was found with both L- and D-isomers. The active peptides also inhibited the increased adherence induced by low-dose calcium loading of normal red blood cells. Finally, a monoclonal antibody against an active peptide specifically immunostained a fraction of sickle cells. These findings implicate a role for band 3 in at least one type of sickle cell adhesiveness via the exposure of normally cryptic membrane sites.