Plasma membrane phospholipid organization in human erythrocytes.

By weight, phospholipids make up approximately 25% of the plasma membrane of mature human erythrocytes. The four major phospholipid species present in the membrane (PC, PE, PS, and SM) are distributed asymmetrically across the bilayer leaflet resulting in an enrichment of choline-phospholipid (PC and SM) in the outer leaflet and of amino-phospholipid (PE and PS) in the cytoplasmic leaflet. This asymmetric organization is preferentially maintained through complex, and at present, poorly understood noncovalent interactions between specific membrane lipids and proteins (in particular, a stabilizing role for the skeletal protein spectrin and band 4.1 have been implicated), although other considerations such as phospholipid net charge, size, and degree of acyl chain unsaturation may also be involved. In certain red cell pathologies, or following experimental manipulation, there is a partial loss of this asymmetry (summarized in Tables XVI, XVII) often resulting in increases in the outer leaflet content of amino-phospholipids and subsequent expression of altered membrane surface properties. Some of these abnormal properties may have pathophysiologic consequence; indeed, red cell membranes displaying increased levels of surface amino-phospholipids have been shown to be potent procoagulants and demonstrate enhanced intermembrane interactions with both model (liposomes) and biologic (mononuclear phagocytes) membranes. Redistribution of membrane phospholipids may not occur homogeneously throughout an entire leaflet but may be restricted to specific membrane regions. These studies strongly suggest that the maintenance of phospholipid asymmetry in human red cell membranes is not a trivial event but probably represents a homeostatic mechanism, the failure of which may lead to alterations in normal erythrocyte functions, and ultimately, survival.