Removal of Old and Abnormal Red Blood Cells from Circulation: Mechanical and Immunologic Mechanisms

Abstract

Normal human red blood cells have a life span of approximately 120 days, at the end of which they are removed from circulation [33]. A main site for the removal of red cells is the spleen, where red cells with abnormal shape or with rigid inclusion bodies cannot pass through the narrow slit pores located between the endothelial cells of the sinus vessels [6, 21]. After removal of the spleen the peripheral blood is characterized by the occurrence of a population of abnormal erythrocytes containing precipitates of hemoglobin (termed Heinz bodies). However, splenectomy does not interfere with the normal turnover of red cells. Thus a further mechanism must exist which is able to distinguish between mature and senescent red cells. Evidence for age-related changes includes increase in the density of old red cells [8, 9], reduction in the concentration of phospholipids and cholesterol [43, 44], reduction in sialic acid residues [7, 15], and reduction in the level of some intracellular metabolites and enzymes [22]. However, none of these changes has been demonstrated to cause specific removal of red cells. On the other hand, there is good evidence that naturally occurring autoantibodies bind to the surface of senescent red cell [1, 23–25, 29–31] and promote their phagocytosis by macrophages [23–25].