Platelet Membrane Glycoproteins, Softcover reprint of the original 1st ed. 1985

It was just about ten years ago that platelet membrane glycoproteins were first charac­ terized and their abnormalities in congenital bleeding disorders first recognized. Dur­ ing this decade there has been a remarkable growth in our understanding of the structure and membrane organization of the platelet surface glycoproteins, their in­ teractions with external ligands during the process of hemostasis, and their defects causing hemorrhagic disease. These studies have advanced the knowledge of platelet involvement in hemostasis from a cellular to a molecular level, and they have provided a model for contact interactions among other cell types. This seemed a proper time to ask those who contributed major observations and insights during these past years to review their progress and to assess the state of our present knowledge. We have planned this volume to begin with the biochemistry of platelet membrane glycoproteins themselves and proceed through their involvement in platelet function to the final considerations of the platelet's role in maintaining the integrity of the vascular system. Our aim was an integrated presentation on the blood platelet from the perspective of its highly specialized and reactive cell surface. James N. George Alan T. Nurden David R. Phillips vii Contents I. INTRODUCTION 1. Plasma Membrane Receptors and Platelet Response Ernst F. Wscher 1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2. Platelet Receptor Functions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 . . . . . . . . . . 2. 1. Receptors Involved in Platelet Adhesion and in Cell-Cell Contact. . . 5 2. 2. Receptors Involved in Platelet Activation. . . . . . . . . . . . . . . . . . . 6 . . . . 3. Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 II.

I. Introduction.- 1. Plasma Membrane Receptors and Platelet Response.- 1. Introduction.- 2. Platelet Receptor Functions.- 2.1. Receptors Involved in Platelet Adhesion and in Cell-Cell Contact.- 2.2. Receptors Involved in Platelet Activation.- 3. Conclusion.- References.- II. Plasma Membrane and Membrane Glycoprotein Structure and Function.- 2. Structural and Molecular Properties of Platelet Membrane Systems.- 1. Introduction.- 2. Ultrastructural Definitions of the Different Platelet Membrane Systems.- 2.1. Platelet Origin in Megakaryocytes.- 2.2. Heterogeneity of Circulating Platelets.- 2.3. Platelet Surface Membranes.- 2.4. The Dense Tubular System and Internal Organelles.- 2.5. Membrane-Associated Components.- 2.6. Characteristics of Internal Membranes.- 3. Platelet Subcellular Fractionation and Membrane Isolation Procedures.- 3.1. Ideals and Practical Considerations.- 3.2. Platelet Isolation.- 3.3. Platelet Lysis and Fractionation of Subcellular Components.- 3.4. Identification of Subcellular Fractions.- 4. Differential Isolation of Platelet Membrane Subfractions.- 5. Free-Flow Electrophoresis for the Separation of Platelet Surface and Intracellular Membranes.- 5.1. Initial Characterization of the System.- 5.2. Isolation of Different Membrane Fractions.- 6. Characterization of Electrophoretically Separated Surface and Intracellular Membranes.- 6.1. Protein and Glycoprotein Composition.- 6.2. Lipid Composition.- 6.3. Enzyme Activities Associated with Phospholipid and Arachidonic Acid Metabolism in Intracellular Membranes.- 7. Conclusions and Comments.- References.- 3. Glycoproteins of the Platelet Plasma Membrane.- 1. Introduction.- 2. Analytical Methods.- 2.1. Early Approaches and Nomenclature.- 2.2. Improved Separations.- 2.3. Nomenclature.- 2.4. Oligosaccharide Chains.- 2.5. Determination of the Molecular Weights of Glycoproteins.- 3. Detection Techniques.- 3.1. Staining Methods.- 3.2. Surface-Labeling Methods.- 3.3. Silver-Staining Methods.- 3.4. Use of 125I-Labeled Lectins to Identify Platelet Glycoproteins on Polyacrylamide Gels.- 4. Methods of Isolation of Platelet Glycoproteins.- 4.1. Lectin Affinity-Chromatography.- 4.2. Immunoabsorption Systems.- 5. Isolation Methods, Structure, and Properties of Individual Platelet Membrane Glycoproteins.- 5.1. Glycoprotein Ib.- 5.2. The Glycoprotein IIb-IIIa Complex.- 5.3. Glycoprotein IIIb.- 5.4. Glycoprotein V.- 5.5. Glycoproteins Ia, Ic, Id, IIa, and Other Glycoprotein Ib Region; Glycoproteins.- 5.6. Glycoproteins in the Glycoprotein IIb-IIIa Region.- 5.7. Glycoproteins in the 43,000- to 70,000-Dalton Region.- 5.8. Glycoproteins of Low Molecular Weight (Less than 43,000).- 5.9. "High-Molecular-Weight" Glycoproteins.- 6. Conclusion.- References.- 4. Organization of Glycoproteins within the Platelet Plasma Membrane.- 1. Introduction.- 2. Glycoproteins IIb-IIIa.- 2.1. Initial Detection of the Glycoprotein IIb-IIIa Complex in Platelet Lysates.- 2.2. Glycoprotein IIb-IIIa and Fibrinogen.- 2.3. Organization of Glycoprotein IIb and Glycoprotein IIIa in Unstimulated and Stimulated Platelets.- 3. Glycoprotein Ib.- 3.1. Glycoprotein Ib Associations in Detergent Lysates.- 3.2. Glycoprotein Ib Organization in the Intact Platelet Membrane.- 3.3. High-Molecular-Weight Forms of Glycoprotein Ib.- 4. Other Glycoprotein Associations?.- 5. Summary.- References.- 5. Structure and Function of Platelet Membrane Glycoproteins as Studied by Crossed Immunoelectrophoresis.- 1. Introduction.- 1.1. General.- 1.2. Crossed Immunoelectrophoresis.- 2. Identification of Antigens.- 2.1. General.- 2.2. Monospecific Antibodies.- 2.3. Purified Antigens.- 2.4. Identification of Antigens by Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) of Excised Immunoprecipitates.- 2.5. Identification of Antigens by the Use of Radioactively Labeled Antibodies.- 3. Characterization of Antigens by CIE.- 3.1. Identification of Amphiphilic Proteins.- 3.2. Carbohydrate-Related Reactions of Glycoproteins.- 3.3. Macromolecular Interactions.- 3.4. Proteolytic Precursor-Product Relationships.- 4. Supramolecular Organization.- 4.1. Absorption of Antibodies.- 4.2. Subcellular Localization.- 4.3. Functional Integrity of Antigens.- 4.4. Binding of Ligands and Identification of Receptors.- 4.5. Metal-Binding Proteins.- References.- 6. Platelet Membrane Electrical Potential: Its Regulation and Relationship to Platelet Activation.- 1. Introduction.- 2. Platelet Membrane Potential.- 2.1. Resting Potential of the Platelet Membrane.- 2.2. Effect of Platelet-Activating Agents on Platelet Membrane Potential.- 2.3. Effect of Platelet Membrane Potential on the Sensitivity of Platelets to Activating Agents.- 3. Intracellular pH in Platelets.- 4. Platelets and Cation Flux.- 4.1. Ca2+ Influx via the Plasma Membrane.- 4.2. Ca2+ Mobilization from Inner Face of Plasma Membrane.- 4.3. Mobilization of Ca2+ from the Dense Tubular System.- 4.4. Removal of Calcium from the Cytoplasm and Calcium Efflux.- 4.5. Na+ and K+ Movement across the Platelet Membrane.- 5. Serotonin Transport.- 5.1. Serotonin Transport across the Plasma Membrane.- 5.2. Serotonin Transport across the Dense Granule Membrane.- 6. Conclusion.- References.- III. Interaction of Platelet Membrane Glycoproteins With The Extracellular Environment.- 7. Receptors for Platelet Agonists.- 1. Introduction.- 2. Thrombin.- 2.1. Thrombin-Platelet Interactions.- 2.2. Glycoprotein V Hydrolysis.- 2.3. Equilibrium Binding of Thrombin to Platelets.- 2.4. Covalent Linkage of Thrombin to Platelets.- 2.5. Thrombin Receptors on Other Cells.- 2.6. Summary.- 3. Adenosine Diphosphate.- 3.1. Functional ADP Receptors.- 3.2. Equilibrium Binding of ADP to Platelets.- 3.3. Identification of ADP-Binding Proteins.- 3.4. Summary.- 4. Collagen.- 4.1. Platelet-Activating Collagens.- 4.2. Measurement of Platelet-Collagen Interactions.- 4.3. The Search for the Collagen Receptor.- 4.4. Summary.- 5. Epinephrine.- 5.1. Classification of Epinephrine Receptors.- 5.2. Ligand Binding to ?-Adrenergic Receptors.- 5.3. Solubilization of ?-Adrenergic Receptors.- 5.4. ?-Adrenergic-Mediated Responses.- 5.5. Identification of ?-Adrenergic Receptors.- 5.6. Summary.- 6. Conclusions.- References.- 8. Secreted Alpha Granule Proteins: The Race for Receptors.- 1. Introduction.- 2. Overview of Alpha Granules.- 2.1. Morphologic Description.- 2.2. Alpha Granule Membranes.- 2.3. Alpha Granule Contents.- 2.4. Functions of Alpha Granule Proteins.- 2.5. Genesis of Alpha Granules and Alpha Granule Contents.- 3. Alpha Granule Secretion.- 3.1. Overview.- 3.2. Secretion of Alpha Granules by Platelets in Suspension.- 3.3. Secretion of Alpha Granules in Response to Contact Activation.- 3.4. Comparison of Alpha Granule Secretion and Dense Granule Secretion.- 4. Interactions of Alpha Granule Proteins with the Surface of Activated Platelets.- 4.1. Interactions of Alpha Granule Proteins with Suspended Platelets.- 4.2. Interactions of Alpha Granule Proteins with Spread Platelets.- 4.3. Mechanism of Binding of Alpha Granule Proteins to Activated but Not Unactivated Platelets: The Rainforest Hypothesis.- References.- 9. The Platelet-Fibrinogen Interaction.- 1. Introduction.- 2. The Fibrinogen Molecule.- 2.1. Plasma Fibrinogen.- 2.2. Platelet Fibrinogen.- 3. Characterization of the Platelet Fibrinogen Receptor.- 3.1. Fibrinogen Binding to ADP-Stimulated Platelets.- 3.2. Fibrinogen Binding Stimulated by Agonists other than ADP.- 3.3. Divalent Cation Requirements for Fibrinogen Binding.- 3.4. Control Mechanisms for Fibrinogen Receptor Exposure.- 3.5. Sites on the Fibrinogen Molecule Interacting with the Fibrinogen Receptor.- 3.6. Interaction of Platelets with Fibrin.- 4. Identification of the Platelet Fibrinogen Receptor.- 4.1. Studies of Fibrinogen Binding to Thrombasthenic Platelets.- 4.2. Photoaffinity Labeling.- 4.3. Platelet-Specific Monoclonal Antibodies.- 4.4. Experiments Using Platelet Extracts.- 5. Summary and Conclusion.- References.- 10. Platelet-von Willebrand Factor Interactions.- 1. Introduction.- 2. Biosynthesis, Localization, and Structure of von Willebrand Factor.- 2.1. Tissue Distribution of von Willebrand Factor.- 2.2. Platelet-Associated von Willebrand Factor.- 2.3. Structure of von Willebrand Factor.- 2.4. Biosynthesis of von Willebrand Factor.- 3. Von Willebrand’s Disease.- 3.1. Type I von Willebrand’s Disease.- 3.2. Type IIA von Willebrand’s Disease.- 3.3. Type IIB von Willebrand’s Disease.- 3.4. Abnormalities of VWF Carbohydrate Composition in von Willebrand’s Disease.- 3.5. Abnormalities of VWF Multimer Formation.- 3.6. Pseudo-von Willebrand’s Disease.- 4. Von Willebrand Factor-Dependent Platelet Function.- 4.1. Platelet Retention.- 4.2. Platelet Agglutination and Aggregation.- 4.3. ExVivo Models of Platelet Adhesion to the Vessel Wall.- 4.4. Correlation among von Willebrand Factor-Dependent Platelet Functions.- 5. Von Willebrand Factor in Nonhemorrhagic Diseases.- References.- 11. Molecular Mechanisms of Platelet Adhesion and Platelet Aggregation.- 1. Primitive Cell Systems.- 2. Platelet Disorders and Insights into Functional Membrane Domains.- 3. Adhesion: The Platelet VWF-Subendothelial Axis.- 3.1. Von Willebrand Factor.- 3.2. Von Willebrand Factor Receptor on Platelets.- 4. Aggregation: Glycoprotein IIb-IIIa and Fibrinogen.- 5. Secondary Aggregation Mechanisms.- References.- 12. Lectin-Carbohydrate Binding as a Model for Platelet Contact Interactions.- 1. Introduction.- 2. Discovery of the Endogenous Platelet Lectin.- 3. Surface-Bound versus Soluble Lectin.- 4. Regulation of Lectin Expression.- 5. Lectin Activity in Inherited Bleeding Disorders.- 6. Identification of the Lectin.- 7. Receptors for the Platelet-Derived Lectin.- 8. Role of the Lectin in Platelet Aggregation.- References.- IV. Interactions of Platelet Membrane Glycoproteins with the Intracellular Cytoskeleton.- 13. The Organization of Platelet Contractile Proteins.- 1. Introduction.- 2. Properties of Platelet Contractile Proteins.- 2.1. Actin.- 2.2. Myosin.- 2.3. Other Actin-Associated Proteins.- 3. Stimulus-Dependent Changes in Contractile Proteins.- 3.1. Polymerization of Actin during Platelet Stimulation.- 3.2. Structural Reorganization of Actin Filaments during Platelet Stimulation.- 4. Regulation of Stimulus-Induced Actin Polymerization.- 4.1. Regulation of the Filament Content of Unstimulated Platelets.- 4.2. Regulation of the Filament Content of Activated Platelets.- 5. Regulation of Stimulus-Induced Reorganization of Actin Filaments.- 5.1. Modification of Myosin during Platelet Activation.- 5.2. Modification of Actin-Binding Protein during Platelet Activation.- 6. Membrane Attachment Sites.- 7. Conclusions.- References.- 14. The Mechanism of Clot Retraction.- 1. Introduction.- 2. Measurement of Contractile Force.- 3. Mechanical Aspects of Platelet-Fibrin Interaction.- 4. Ultrastructure and Tension Generation in Contracted Clots.- 4.1. Normal Clots.- 4.2. Thrombasthenic and Storage-Pool-Deficient Clots.- 4.3. Factor XIII-Deficient Clots.- 5. Activators and Inhibitors of Clot Retraction.- 5.1. Divalent Cations.- 5.2. Prostaglandin Metabolites.- 5.3. Cytoskeletal Destabilizing Agents.- 5.4. Energy Metabolism Inhibitors.- 6. Transmembrane Linkage of Cytoskeletal Components with Fibrin.- 7. Regulation of the Cytoskeletal Apparatus and Model of Clot Retraction.- 8. Concluding Remarks.- References.- V. Platelet Membrane Glycoprotein Immunology and Abnormalities.- 15. Immunology of the Platelet Surface.- 1. Introduction.- 2. Methods for Detection of Platelet Antigens and Their Antibodies.- 3. Platelet-Associated Antigens.- 3.1. Blood Group Antigens.- 3.2. HLA Antigens.- 3.3. Tn and T (Thomsen-Friedenreich) Antigens.- 4. Platelet-Specific Antigens.- 4.1. Alloantigens.- 4.2. The Receptor for Drug-Dependent Antiplatelet Antibodies.- 4.3. Autoantigens.- 4.4. Isoantigens.- 5. Platelet Reactions with Immunoglobulins at Other than the Antigen-Specific Site.- 5.1. The Fc Receptor.- 5.2. Role of Complement in Activation of Human Platelets.- 6. Clinical Conditions Arising from Immunologically Mediated Platelet Damage.- 6.1. Alloantibodies.- 6.2. Thrombocytopenia as a Result of Drug Ingestion.- 6.3. Idiopathic Thrombocytopenic Purpura (ITP).- 6.4. Disease-Associated Immune Thrombocytopenia.- 7. Conclusion.- References.- 16. Glycoprotein Defects Responsible for Abnormal Platelet Function in Inherited Platelet Disorders.- 1. Introduction.- 2. Bernard-Soulier Syndrome.- 2.1. Platelet Function.- 2.2. Surface Charge Deficiency.- 2.3. Membrane Glycoprotein Ib Deficiency.- 2.4. 125I-Labeling of the Bernard-Soulier Platelet Surface.- 2.5. Crossed Immunoelectrophoresis.- 2.6. Use of High-Resolution Two-Dimensional Polyacrylamide Gel Electrophoresis.- 2.7. 3H-Labeling of the Bernard-Soulier Platelet Surface.- 2.8. Glycoprotein V Deficiency.- 2.9. Heterogeneity within Bernard-Soulier Syndrome.- 2.10. Problems of Analyzing Bernard-Soulier Platelet Glycoproteins.- 2.11. Monoclonal Antibodies.- 2.12. Basic Genetic Lesion in Bernard-Soulier Syndrome.- 2.13. Conclusions on Bernard-Soulier Syndrome.- 3. Gray Platelet Syndrome.- 3.1. Platelet Function.- 3.2. Protein and Glycoprotein Deficiencies.- 3.3. Abnormalities in Megakaryocytes.- 3.4. Significance of the Protein and Glycoprotein Deficiencies.- 4. Glanzmann’ s Thrombasthenia.- 4.1. Platelet Function.- 4.2. Initial Studies Reporting Deficiencies of Glycoprotein IIb and Glycoprotein IIIa.- 4.3. Surface-Labeling Procedures.- 4.4. Type I and Type II Thrombasthenia.- 4.5. Crossed Immunoelectrophoresis.- 4.6. Patient Heterogeneity.- 4.7. Platelet-Specific Alloantigens.- 4.8. Monoclonal Antibodies.- 4.9. Newly Described Variants with Glanzmann’s Thrombasthenia.- 4.10. Altered Surface Reactivity of Glanzmann’s Thrombasthenic Platelets.- 4.11. Basic Genetic Lesion in Thrombasthenia.- 4.12. Conclusions on Thrombasthenia.- 5. General Conclusions.- References.- VI. Conclusion.- 17. The Role of Membrane Glycoproteins in Platelet Formation, Circulation, and Senescence: Review and Hypotheses.- 1. Introduction.- 2. Megakaryocyte Development in the Marrow.- 2.1. The Origin of Megakaryocytes from Pluripotent Stem Cells.- 2.2. The Development of Megakaryocyte Membrane Systems.- 3. Platelet Production from Megakaryocytes.- 3.1. Megakaryocyte Release from the Marrow and Platelet Release in the Lungs.- 3.2. The Analogy between Platelet Separation from Megakaryocytes and Reversible Aggregation of Mature Platelets.- 3.3. The Origins of Density and Size Heterogeneity of Circulating Platelets.- 3.4. Platelet Size and Platelet Membrane Glycoproteins.- 4. The Function of Circulating Platelets.- 4.1. Transient-Sequestration of Platelets in the Spleen.- 4.2. The Hypothesis of Continual Endothelial Support by Circulating Platelets.- 4.3. Platelet Membrane Fragmentation during Reversible Adhesion Encounters.- 4.4. Platelet Membrane Microparticles.- 5. Platelet Senescence and Removal from the Circulation.- 5.1. The Occurrence of Senescent Antigens.- 5.2. T and Tn Determinants on Glycoprotein Ib as Possible Platelet Senescent Antigens.- References.