Acquisition of Autophagic Vacuoles by Human Erythrocytes Physiological Role of the Spleen
TL;DR: Transfusion studies show that these inclusions can be acquired by normal mature erythrocytes when circulating in an asplenic patient, and suggests that, in the absence of a spleen, autophagic vacuoles may occur in situ in all circulating red cells.
About: This article is published in Blood.The article was published on 1970-11-01. It has received 91 citations till now. The article focuses on the topics: Spleen & Pure red cell aplasia.
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01 Jan 1976
TL;DR: This chapter discusses Lysosome Formation, Functioning and Fate, as well as some General Aspects of the Control and Specificity of Autophagy, which are related to Turnover and Modulation.
Abstract: I. General Considerations and Background.- I.1. Perspectives.- I.2. Definitions.- I.2.1. General Functional Categories.- I.2.2. Outline of Lysosome Functioning in Phagocytes.- I.2.3. Additional Terms: Heterophagy and Autophagy.- I.3. Characterization of Lysosomes.- I.3.1. Basic Biochemical Characteristics of Lysosomes.- I.3.1.1. Key Features of Lysosomes.- I.3.1.2. The Lysosomal Enzymes.- I.3.1.3. Digestion in Lysosomes.- I.3.1.4. Lysosomal "Permeability".- I.3.2. Some Cytochemical and Morphological Characteristics.- I.3.2.1. Cytochemical Methods.- I.3.2.2. Cytochemical Studies of Exogenous Tracers.- I.3.2.3. Additional Cytochemical Features of Lysosomes: "Matrix" Materials and Some Other Non-Enzymatic Components.- I.4. Morphological Categories of Lysosomes.- II. Lysosome Formation, Functioning and Fate.- II. 1. Heterophagy.- II.1.1. Background.- II.1.2. Specificity.- II.1.3. The Transport of Acid Hydrolases.- II.1.3.1. The Formation of Primary Lysosomes in PMN Leukocytes.- II.1.3.2. Primary Lysosomes in Macrophages.- II.1.4. Fusion Phenomena, Lysosome "Reuse" and Lysosome Membranes.- II.1.4.1. Lysosome "Recycling".- II.1.4.2. Energetics and Control of Movements in Heterophagy.- II.1.4.3. Lysosome Membranes Fusion.- II.1.4.4. Other Features of the Lysosome Surface: Enzymes, Changes and Stability.- II.1.4.5. Acidification.- II.2. Hydrolase Transport in Cells Other than Phagocytes.- II.2.1. GERL.- II.2.2. Endoplasmic Reticulum and Lysosomes Some Biochemical Findings.- II.3. Autophagy.- II.3.1. Basic Morphology.- II.3.2. Mode of Formation of Autophagie Vacuoles.- II.3.2.1. Source of the Delimiting Membranes.- II.3.2.2. Source of the Hydrolases.- II.3.3. Crinophagy.- II.3.4. Some General Aspects of the Control and Specificity of Autophagy.- II.4. Multivesicular Bodies (MVB's).- II.4.1. Heterophagic Roles.- II.4.2. Participation in Autophagy.- II.4.2.1. Incorporation of Secretory Material and of Intact Vesicles.- II.4.2.2. Degradation of Membranes Participating in Endocytosis.- II.4.2.3. Possible Roles in Degrading Other Types of Membrane.- II.4.2.4. Microautophagy.- II.5. The Fate of Lysosomes.- II.5.1. Release vs. Retention.- II.5.2. "Telolysosomes" and Lipofuscin.- II.6. Lysosome Heterogeneity.- III. Lysosomes in Turnover and Modulation.- III.1. Turnover of Cells and Tissues of Higher Animals and Features of Developmental Remodelling.- III.1.1. Background and an Example: The Red Blood Cell Life History.- III.1.1.1. Lysosomes in the Maturation of Red Blood Cells.- III.1.1.2. The Destruction of Red Blood Cells.- III.1.1.3. Iron Storage and Release.- III.1.2. Developmental "Remodelling".- III.1.2.1. Case Histories: Cell Destruction in Insect Metamorphosis.- III.2. Turnover of Extracellular Materials.- III.2.1. Connective Tissue Components.- III.2.1.1. Hydrolase Release in Cartilage.- III.2.1.2. Osteoclasts.- III.2.1.3. Collagenases.- III.3. Turnover of Circulating Macromolecules.- III.3.1. Selectivity.- III.4. Intracellular Turnover.- III.4.1. Some Methodological Perspectives and Problems.- III.4.2. Turnover in Bacteria.- III.4.3. Turnover of Organelles and Intracellular Macromolecules in Eucaryotes.- III.4.3.1. Some General Points and Some Experiments Paralleling those Done with Procaryotes.- III.4.3.2. Turnover of Macromolecules that are not Components of Membrane-Delimited Organelles.- III.4.3.3. Aspects of the Turnover of Membrane-Delimited Cytoplasmic Organdies.- III.5. Turnover of Photoreceptor Membranes.- IV. Pathology.- IV.1. Lysosomal Storage Diseases.- IV.1.1. Lipidoses and Polysaccharidoses.- IV.1.2. Etiological Aspects.- IV.1.3. Some Interesting Disorders of Uncertain Status.- IV.2. Lysosomes and Infection.- IV.2.1. The Entry of Structures with Macromolecular Dimensions into Cells: Viruses and Toxic Proteins.- IV.2.2. Potentially Instructive Failures of Defenses.- IV.2.3. Malaria.- IV.3. The "Pathological" Release of Enzymes to Extracellular Spaces Arthritis, Inflammation, and Related Phenomena.- IV.4. The Intracellular Release of Hydrolases: Lysosome Fragility, Labilizers, and Stabilizers.- IV.4.1. Methodological Problems.- IV.4.2. Silica and Uric Acid.- IV.4.3. Labilizers, Stabilizers, Drugs, and Inhibitors.- IV.5. Lysosomes in Immune Responses.- IV.5.1. Macrophages and Some Other Cells in the "Processing" or "Presentation" of Antigens.- IV.5.2. Lysosomes in Lymphocyte Activation.- IV.5.3. The Transfer of Maternal Antibodies.- V. Some Special Topics and Some Loose Ends.- V.1. Lysosomes in Plant Cells.- V.1.1. Senescence and Cell Death.- V.1.2. Autophagy.- V.1.3. Extracellular Hydrolases.- V.2. Hydrolases in Secretory Cells.- V.2.1. Lysosomes and Secretory Processes the Thyroid Gland.- V.2.2. Hydrolases in the Golgi Apparatus and Secretion Granules.- V.2.3. Melanin.- V.3. Lysosomes in Animal Gametes.- V.3.1. Sperm.- V.3.2. Eggs.- V.4. Closing Comments.- Acknowledgements.
204 citations
TL;DR: Understanding the modulators of organelles clearance in erythropoiesis may elucidate the pathogenesis of different dyserythropOietic diseases such as myelodysplastic syndrome, leukemia and anemia.
Abstract: Erythropoiesis occurs mostly in bone marrow and ends in blood stream. Mature red blood cells are generated from multipotent hematopoietic stem cells, through a complex maturation process involving several morphological changes to produce a highly functional specialized cells. In mammals, terminal steps involved expulsion of the nucleus from erythroblasts that leads to the formation of reticulocytes. In order to produce mature biconcave red blood cells, organelles and ribosomes are selectively eliminated from reticulocytes as well as the plasma membrane undergoes remodeling. The mechanisms involved in these last maturation steps are still under investigation. Enucleation involves dramatic chromatin condensation and establishment of the nuclear polarity, which is driven by a rearrangement of actin cytoskeleton and the clathrin-dependent generation of vacuoles at the nuclear-cytoplasmic junction. This process is favored by interaction between the erythroblasts and macrophages at the erythroblastic island. Mitochondria are eliminated by mitophagy. This is a macroautophagy pathway consisting in the engulfment of mitochondria into a double-membrane structure called autophagosome before degradation. Several mice knock-out models were developed to identify mitophagy-involved proteins during erythropoiesis, but whole mechanisms are not completely determined. Less is known concerning the clearance of other organelles, such as smooth and rough ER, Golgi apparatus and ribosomes. Understanding the modulators of organelles clearance in erythropoiesis may elucidate the pathogenesis of different dyserythropoietic diseases such as myelodysplastic syndrome, leukemia and anemia.
198 citations
Cites background from "Acquisition of Autophagic Vacuoles ..."
...The exocytosis of this vesicle might be favored by the spleen, as splenectomized patients present large vacuoles inside reticulocytes (Holroyde and Gardner, 1970)....
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01 Jan 1974
TL;DR: In this paper, it is shown that each biological membrane operates differentially on the two compartments it separates and is thus anisotropic in its function, and that the molecular constituents of the two surfaces differ and that this asymmetry constitutes a principal feature of membrane organization.
Abstract: Each biological membrane operates differentially on the two compartments it separates and is thus anisotropic in its function. It is reasonable to suppose that the molecular constituents of the two surfaces differ and that this asymmetry constitutes a principal feature of membrane organization. Since membranes are only a few macromolecules thick, it is clear that enumeration of the components at each surface would do much to define the structure as a whole.
191 citations
TL;DR: A multitrack dehydration model based on interactive influences between the red cell anion exchanger and two K(+) transporters, the Gardos channel (hSK4, hIK1) and the K-Cl cotransporter (KCC), with differential effects dependent on red cell age and variability of KCC expression among reticulocytes is presented.
Abstract: Polymers of deoxyhemoglobin S deform sickle cell anemia red blood cells into sickle shapes, leading to the formation of dense, dehydrated red blood cells with a markedly shortened life-span. Nearly...
162 citations
Cites background from "Acquisition of Autophagic Vacuoles ..."
...There had been earlier reports showing vesicular accumulation within RBCs of splenectomized persons (141)....
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TL;DR: It is shown that the final stage of reticulocyte maturation occurs by a previously undescribed mechanism in which large glycophorin A-containing vesicles forming at the cytosolic face of the plasma membrane are internalized and fuse with autophagosomes before expulsion of theAutophagosomal contents by exocytosis.
160 citations
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Journal Article•
8,559 citations
Journal Article•
5,201 citations
TL;DR: Certain hitherto unobserved details are revealed and some sort of specificity exists, although the factors involved are not yet understood.
Abstract: Heavy metals may be incorporated from solution into tissue sections for electron microscopy The resulting increase in density of the tissue provides greatly enhanced contrast with minimal distortion Relative densities of various structures are found to depend on the heavy metal ions present and on the conditions of staining Certain hitherto unobserved details are revealed and some sort of specificity exists, although the factors involved are not yet understood
4,040 citations
TL;DR: It is thought that in these highly alkaline staining solutions lead is present as an hydroxide complex anion (plumbite ion) and that this anion is responsible for the staining, and the methods of preparation are based on this hypothesis.
Abstract: The lead hydroxide stain of Watson (1958) used for increasing contrast in thin sections for electron microscopy has found acceptance in many laboratories. However, this stain has an unfortunate tendency to form precipitates (probably of lead carbonate (5)) on exposure to the air, thus contaminating the sections and irritating the observer. This drawback has led to the development of several modifications (2, 3) of the original method of staining and the use of ingenious devices (4, 5) for preventing exposure to air and consequent precipitate formation. We offer the following alternative methods which, we believe, are simpler to perform than those hitherto described. They have the additional advantages mentioned below. The methods are based on the observation that highly alkaline solutions of lead salts (pH > 11.5) yield relatively stable solutions which stain rapidly and intensely, thus obviating the hazard of precipitation to a marked degree. The methods have these additional advantages: the staining solutions are easily and rapidly prepared, are simply stored, and are stable for long periods of time. Furthermore, they can be efficiently used, many grids being treated simultaneously, without excessive precautions being taken against lead carbonate precipitation. Finally, \"difficult\" material, embedded in media which characteristically yield rather low contrast, such as epoxide resins, can be rapidly and easily stained. \"C lean\" preparations, of high contrast, are routinely obtained. As will be discussed later, it is thought that in these highly alkaline staining solutions lead is present as an hydroxide complex anion (plumbite ion) and that this anion is responsible for the staining. The methods of preparation are based on this hypothesis. Two methods for preparing the staining solutions have been found useful:
1,298 citations