Relationship between Drug-and Phospholipase-Induced Shape Changes of Human Erythrocytes

Abstract

Invagination or crenation of human erythrocytes induced by pretreating the cells with an invaginator or crenator was reversed by treatment with phospholipase A₂ (from bee venom) or phospholipase C (from Clostridium perfringens), respectively, under non-hemolytic conditions. In this study, flurbiprofen and lysophosphatidylcholine were used as crenators, and chlorpromazine and cepharanthine were used as invaginators. Crenation or invagination induced by pretreating the erythrocytes with phospholipase A₂ or phospholipase C, which attacks mainly phosphatidylcholine in the outer layer of the membrane lipid bilayer, was also reversed by treatment with an invaginator or crenator, respectively. We also found that pretreatment of the erythrocytes with any of the drugs tested does not significantly affect the susceptibility of the cells to the phospholipases, and also that pretreatment of the erythrocytes with any of the phospholipases used does not affect the binding of the drug to the cells. Thus, the findings suggest that the shape change of human erythrocytes induced by amphiphilic drugs occurs through a mechanism similar to that by which the shape change due to partial hydrolysis of the outer layer phospholipids by phospholipase action occurs, possibly through a change in the lipid bilayer balance of the membrane.