The selective and conjoint loss of red cell lipids

The pattern of lipid loss from the membrane of red cells incubated in serum is influenced by the availability of glucose. Under homeostatic conditions with respect to glucose, cholesterol alone is lost. This results from esterification of free cholesterol in serum by the serum enzyme, lecithin:cholesterol acyltransferase, and is associated with a proportional decrease in membrane surface area, reflected by an increased osmotic fragility. This selective loss of membrane cholesterol also occurs in hereditary spherocytosis (HS) red cells, even after incubation for 65 hr in the presence of glucose. The loss of free cholesterol from red cells relative to its loss from serum, under these conditions, is greatest at higher hematocrits, similar to those found in the spleen. Although the selective loss of membrane cholesterol increases the spherodicity of normal red cells, it does not lead to a change in their rate of glucose consumption, and both the loss of cholesterol and the increase in osmotic fragility are reversible in vitro. Moreover, normal red cells made osmotically fragile by cholesterol depletion in vitro rapidly become osmotically normal and survive normally after their reinfusion in vivo.In contrast to this selective loss of membrane cholesterol, red cells incubated in the absence of glucose lose both cholesterol and phospholipid. This occurs more rapidly in HS than normal red cells and is followed by a disruption of cation gradients and then by hemolysis. Cholesterol and phospholipid lost under these conditions is not restored during subsequent incubations in vitro. Selective loss of membrane cholesterol is a physiologic event secondary to an altered state of serum lipids. It is reversible both in vitro and in vivo and neither influences cellular metabolism nor impairs viability. Conjoint loss of phospholipid and cholesterol, however, results from intrinsic injury to the red cell membrane which results from prolonged metabolic depletion.