RGD-containing ankyrin externalized onto the cell surface triggers αVβ3 integrin-mediated erythrophagocytosis

The RGD motif on the extracellular matrix or cell surface, together with its integrin receptors, constitutes a major recognition system for cell adhesion. There are several erythrocyte major membrane skeletal proteins, e.g., α spectrin, ankyrin, and protein 4.2, that bear an RGD motif. However, it is not known whether the RGD/integrin recognition system is utilized in the erythrocyte-macrophage adhesion during erythrophagocytosis. Here we report that the RGD motif of ankyrin, but not others, is recognized by the αvβ3 integrin receptor. In addition, the RGD motif of ankyrin, a peripheral membrane protein, can be externalized onto the cell surface when erythrocytes are incubated with calcium and sheared both at physiological levels. Furthermore, the erythrocyte-macrophage adhesion can be specifically inhibited by ankyrin and/or αvβ3. Thus, externalization of ankyrin followed by RGD/integrin recognition may be a novel mechanism by which erythrocytes adhere to macrophages preceding phagocytosis.

► The RGD motif of erythrocyte ankyrin binds to αvβ3 integrin.
► Ankyrin can be externalized onto the erythrocyte cell surface with physiological Ca2+ and shear.
► The RGD motif of ankyrin on erythrocytes can be recognized by αvβ3 integrin on macrophages.
► RGD/αvβ3 recognition may be a novel mechanism by which aged or diseased erythrocytes are phagocytosed by macrophages.