A basis of the acanthocytosis in inherited and acquired disorders

Abstract

Acanthocytosis refers to the transformation of the normal biconcave disc erythrocyte into one with a few irregularly shaped external projections distributed unevenly at its membrane surface. It is associated with a variety of inherited and acquired disorders. A relationship between the acanthocytosis in chorea-acanthocytosis and an alteration of Band 3, the anion exchange protein, has been previously suggested. We have previously proposed a mechanism of erythrocyte shape control in which decrease and increase of the ratio of the outward-facing (Band 3 o) and inward-facing (Band 3 i) conformations of Band 3 contracts and relaxes the membrane skeleton, thus promoting echinocytosis and stomatocytosis, respectively. The equilibrium Band 3 o/Band 3 i ratio is determined by the Donnan equilibrium ratio of anions and protons, increasing with the increase of the Donnan ratio. Based on the evidence suggesting that the acanthocyte and echinocyte are interrelated, the mechanism could explain by a decrease of the Donnan ratio the occurrence of acanthocytes in pyruvate kinase and pyrimidine 5 ′-nucleotidase deficiencies, dehydrated hereditary stomatocytocytosis, In(Lu) phenotype, chorea-acanthocytosis, and McLeod phenotype. Consistent with the proposed mechanism indicating that the membrane skeleton is an important determinant of the erythrocyte shape, is the alteration of its conformation in chorea-acanthocytosis, McLeod phenotype and Fanconi’s anemia. In agreement with the proposed mechanism indicating that Band 3 conformation controls the erythrocyte shape are the occurrence of an acanthocytosis in individuals expressing the rare Band 3 HT variant and of alterations of Band 3 properties in chorea-acanthocytosis and In(Lu) phenotype. The observations that the lipid composition or organization are normal in chorea-acanthocytosis and McLeod phenotype are supportive of the proposed mechanism since it postulates that the lipid bilayer has a secondary role in determining the erythrocyte shape. The acanthocytoses in alcoholic cirrhosis and abetalipoproteinemia are accompanied by significant increases of the cholesterol level and of the ratio of sphingomyelin and glycerophospholipids, respectively. However, they could occur by a change of the Band 3 conformation since cholesterol binds specifically to Band 3 and inhibits its anion transport activity, and that sphingomyelin potentiates this inhibition. Thus, the acanthocytosis could involve an alteration of the Band 3 conformation.