Erythrocyte: Programmed Cell Death

Erythrocytes are produced by a complex and finely regulated process of erythropoiesis. It starts with a pluripotential stem cell that, in addition of its self replication capacity, can give rise to separate cell lineages. Erythropoiesis passes from the stem cell through the multipotent progenitor CFU-GEMM (colony-forming unit granulocyte erythroid monocyte and megakaryocyte), and then BFU-E (burst-forming unit erythroid) and CFU-E (colonyforming unit eryhtroid), to the first recognizable erythrocyte precursor in the bone marrow, the pronormoblast. This cell gives rise to a series of progressively smaller normoblasts with increasing content of hemoglobin. The nucleus is finally extruded from the late normoblast leading to mature red blood cell through the reticulocyte stage. Erythropoiesis ends with the mature circulating red cell, which is a non-nucleated biconcave disc, performing its function of oxygen delivery. In this process, the glycoprotein hormone erythropoietin has been known as the major humoral regulator of red cell production. It is now well established that erythropoietin stimulates erythropoiesis, at least in part, by protecting erythroblasts from apoptosis. Human mature erythrocytes are terminally differentiated cells that are devoid of mitochondria, as well as of nucleus and other organelles. In circulation, the red cell is constantly tested for its capacity to undergo marked cellular deformation. This ability to change its shape is essential for optimal cell function, since the resting diameter of the human red cell far exceeds that of the capillaries and splenic endothelial slits through which it must pass (Mohandas & Groner, 1989). A two dimensional network of proteins interacting between transmembrane location and cytoplasmic surface of the plasma membrane gives the red blood cell its properties of elasticity and flexibility that allows the success of this journey. The mature erythrocyte is unable to self-repair and has no capacity to synthesize proteins. Therefore, its lifespan is finite and is shortened further when the cell’s environment becomes hostile or when the erythrocyte’s ability to cope with damaging extracellular influences becomes impaired. The erythrocyte limited lifespan implies that, as in other cells, life and death are well regulated for erythrocytes, in spite of their lack of capacity for protein synthesis (Bosman et al., 2005). In the present review, we aim to show updated information concerning erythrocyte death in order to contribute to the understanding of the physiopathological relationship of this process with the development of anemia.