FREE-RADICAL THEORY OF ERYTHROCYTE AGING

Mature, circulating mammalian erythrocytes have a finite lifespan. The molecular-mechanism that determines removal of cells from the circula tion remains unknown, but probably involves recognition of senescence antigens by phagocytes, either directly or via an antibody/complement- mediated pathway. It has been proposed that the major senescence antig en in aged erythrocytes is derived from the band 3 protein, the main t ransmembrane glycoprotein in erythrocytes. Other possible mechanisms f or red cell aging include mechanical fatigue, ATP depletion, calcium a ccumulation, and the generation of reactive oxygen species (ROS). ROS, which damage proteins and initiate lipid peroxidation, can be generat ed either inside erythrocytes through the hemoglobin oxidation pathway or outside (eg, by stimulated macrophages). The ROS theory of red cel l aging has been widely accepted, yet it lacks direct supporting evide nce. To test this hypothesis, two critical technique have been establi shed in this laboratory. First, we determine the lifespan of erythrocy tes in vivo using a fluorescent cell labeling technique. Second, trans genic mice have been produced which express high levels of the human a ntioxidant enzymes, superoxide dismutase and glucose-6-phosphate dehyd rogenase, in their erythrocytes. These two techniques will be very use ful for the evaluation of the free radical theory of red cell aging.