Harpers

RED & WHITE BLOOD CELLS / 611Pluripotentstem cellInterleukinsGM-CSFCFU-GEMMBFU-E(earlyand late)InterleukinsGM-CSFEpoErythroidprecursorMatureRBCsFigure 52–1. Greatly simplified scheme of differentiation of stem cells to redblood cells. Various interleukins (ILs), such as IL-3, IL-4, IL-9, and IL-11, are involvedat different steps of the overall process. Erythroid precursors include the pronormoblast,basophilic, polychromatophilic, and orthochromatophilic normoblasts,and the reticulocyte. Epo acts on basophilic normoblasts but not on later erythroidcells. (CFU-GEMM, colony-forming unit whose cells give rise to granulocytes,erythrocytes, macrophages, and megakaryocytes; BFU-E, burst-formingunit-erythroid; GM-CSF, granulocyte-macrophage colony-stimulating factor; Epo,erythropoietin; RBC, red blood cell.)The Red Blood Cell Has a GlucoseTransporter in Its MembraneThe entry rate of glucose into red blood cells is fargreater than would be calculated for simple diffusion.Rather, it is an example of facilitated diffusion (Chapter41). The specific protein involved in this process iscalled the glucose transporter or glucose permease.Some of its properties are summarized in Table 52–3.The process of entry of glucose into red blood cells is ofmajor importance because it is the major fuel supply forthese cells. About seven different but related glucosetransporters have been isolated from various tissues; unlikethe red cell transporter, some of these are insulindependent(eg, in muscle and adipose tissue). There isconsiderable interest in the latter types of transporterbecause defects in their recruitment from intracellularsites to the surface of skeletal muscle cells may help explainthe insulin resistance displayed by patients withtype 2 diabetes mellitus.Reticulocytes Are Activein Protein SynthesisThe mature red blood cell cannot synthesize protein.Reticulocytes are active in protein synthesis. Once reticulocytesenter the circulation, they lose their intracellularorganelles (ribosomes, mitochondria, etc) withinabout 24 hours, becoming young red blood cells andconcomitantly losing their ability to synthesize protein.Extracts of rabbit reticulocytes (obtained by injectingrabbits with a chemical—phenylhydrazine—that causesa severe hemolytic anemia, so that the red cells are almostcompletely replaced by reticulocytes) are widelyused as an in vitro system for synthesizing proteins. EndogenousmRNAs present in these reticulocytes aredestroyed by use of a nuclease, whose activity can be inhibitedby addition of Ca 2+ . The system is then programmedby adding purified mRNAs or whole-cell extractsof mRNAs, and radioactive proteins are synthesizedin the presence of 35 S-labeled L-methionine orother radiolabeled amino acids. The radioactive proteinssynthesized are separated by SDS-PAGE and detectedby radioautography.Superoxide Dismutase, Catalase,& Glutathione Protect Blood CellsFrom Oxidative Stress & DamageSeveral powerful oxidants are produced during thecourse of metabolism, in both blood cells and mostother cells of the body. These include superoxide (O 2−⋅),hydrogen peroxide (H 2 O 2 ), peroxyl radicals (ROO • and hydroxyl radicals (OH • ). The last is a particularlyreactive molecule and can react with proteins, nucleicacids, lipids, and other molecules to alter their structureand produce tissue damage. The reactions listed inTable 52–4 play an important role in forming these oxidantsand in disposing of them; each of these reactionswill now be considered in turn.Superoxide is formed (reaction 1) in the red bloodcell by the auto-oxidation of hemoglobin to methemoglobin(approximately 3% of hemoglobin in human redblood cells has been calculated to auto-oxidize per day);in other tissues, it is formed by the action of enzymessuch as cytochrome P450 reductase and xanthine oxidase.When stimulated by contact with bacteria, neutrophilsexhibit a respiratory burst (see below) and producesuperoxide in a reaction catalyzed by NADPHoxidase (reaction 2). Superoxide spontaneously dismutatesto form H 2 O 2 and O 2 ; however, the rate of thissame reaction is speeded up tremendously by the actionof the enzyme superoxide dismutase (reaction 3). Hydrogenperoxide is subject to a number of fates. The enzymecatalase, present in many types of cells, converts