Biochemistry of Platelets

Biochemistry of Platelets is a comprehensive review of the biochemistry of platelets, with emphasis on the molecular basis for the various biological processes in which they participate. Topics range from stimulus-response coupling mechanisms to platelet contractile proteins, platelet membrane glycoproteins, and storage organelles in platelets and megakaryocytes. The expression and function of adhesive proteins on the platelet surface is also discussed. Comprised of 12 chapters, this book begins with a description of the morphological and metabolic responses to agonists, as well as the involvement of certain processes in the coupling of agonist-receptor interactions to platelet responses. The following chapter deals with platelet arachidonate metabolism and platelet-activating factor, focusing on the release of arachidonate from platelet lipid stores; pathways of platelet arachidonate metabolism and effects of arachidonate metabolites; and inhibition of platelet arachidonate metabolism by aspirin. The structure, function, and modification in disease of platelet membrane glycoproteins are then discussed, along with prothrombin activation on platelets and platelet regulation of thrombus formation. Secreted platelet proteins as markers for pathological disorders are also considered. This monograph is intended as a reference for investigators involved in platelet research as well as a source of information for those working in other areas of biological investigation.

Table of Contents:
Contributors Preface 1. Stimulus-Response Coupling Mechanisms I. Introduction II. Experimental Strategies for Definition of Mechanisms of Stimulus-Response Coupling in Platelets III. Possible Coupling Mechanisms IV. Integration of Coupling Mechanisms References 2. Platelet Arachidonate Metabolism and Platelet-Activating Factor I. Introduction II. Release of Arachidonate from Platelet Lipid Stores III. Pathways of Platelet Arachidonate Metabolism and Effects of Arachidonate Metabolites IV. Inhibition of Platelet Arachidonate Metabolism by Aspirin V. Platelet-Activating Factor References 3. Platelet Contractile Proteins I. Introduction II. Properties of Platelet Contractile Proteins III. Methods of Studying Contractile Proteins within Platelets IV. Contractile Proteins in Unstimulated Platelets V. Contractile Proteins in Activated Platelets VI. Regulation of Activation-Induced Changes in Platelet Contractile Proteins VII. Association of Actin Filaments with Plasma Membranes VIII. Conclusions References 4. Platelet Membrane Glycoproteins: Their Structure, Function, and Modification in Disease I. Introduction II. Identification of Platelet Membrane Glycoproteins III. Properties of the Major Platelet Membrane Glycoproteins IV. Abnormalities of Membrane Glycoproteins in Inherited Platelet Disorders References 5. Expression and Function of Adhesive Proteins on the Platelet Surface I. Introduction II. Mechanisms for Platelet Surface Expression of the Adhesive Proteins III. Common Features of the Platelet Adhesive Proteins IV. Fibrinogen-Platelet Interactions V. Fibronectin-Platelet Interactions VI. Von Willebrand Factor-Platelet Interactions VII. Thrombospondin-Platelet Interactions VIII. Cell Surface Expression of the Adhesive Proteins: Common Features and Interrelationships IX. Summation References 6. Storage Organelles in Platelets and Megakaryocytes I. Introduction II. Platelet Organelles III. Exocytosis IV. Platelet Granule Abnormalities References 7. A Model for Assembly of Coagulation Factor Complexes on Cell Surfaces: Prothrombin Activation on Platelets I. Introduction II. Prothrombinase as a Model for Complex Formation in Coagulation Reactions III. Platelet-Binding Characteristics of Prothrombinase Complex Constituents IV. Role of Platelet Activation in Prothrombinase Complex Assembly and Function V. Cleavage of Factor V and Factor Va by Platelet-Associated Proteases and Factor Xa VI. Regulation of the Platelet-Bound Prothrombinase Complex VII. Summary: Utility of Model Systems References 8. Platelet Regulation of Thrombus Formation I. Platelets and Activation of Coagulation II. Role of Platelets in Events Following Activation of Clotting III. Regulation of Platelet Thrombus Formation by Thrombin and the Fibrinolytic System IV. Unresolved Issues in Platelet Involvement in Blood Clotting References 9. Platelet-Derived Growth Factor: Purification, Characterization, and Role in Normal and Abnormal Cell Growth I. Introduction II. Location of PDGF within Platelets III. Platelets May Contain Growth-Promoting Activity Other than PDGF IV. Properties of Purified PDGF V. Radioimmunoassay of PDGF VI. Specific Covalent Binding of Human Plasma a2-Macroglobulin to Human PDGF VII. PDGF Binds Specifically to the Surface of Target Cells VIII. PDGF Stimulates Tyrosine-Specific Protein Kinase Activity in Target Cells IX. Purification of the PDGF Receptor X. Common Kinase Substrates in Growth Factor-Stimulated and Tumor Virus-Transformed Cells XI. PDGF in Inflammatory and Repair Processes XII. PDGF and Atherosclerosis XIII. PDGF Effects on the Cell Cycle XIV. Relationship of PDGF to the Transforming Protein of the Simian Sarcoma Virus XV. Other Activities of PDGF XVI. Conclusions References 10. Secreted Platelet Proteins as Markers for Pathological Disorders I. Introduction II. Biochemical Characteristics of Platelet Factor 4 and ß-Thromboglobulin III. Biologic Activities of Platelet Factor 4 and ß-Thromboglobulin IV. Radioimmunoassay Measurement of Platelet Factor 4 and ß-Thromboglobulin During in Vitro Secretion V. Measurement of Plasma Concentrations of Platelet Factor 4 and ß-Thromboglobulin to Assess in Vivo Platelet Activation and Secretion VI. Platelet Activation and Secretion in Patients with Cardiac Disease VII. Assessment of Platelet Activation and Secretion in Other Types of Vascular Disease VIII. Miscellaneous Clinical Studies References 11. Megakaryocyte Biochemistry I. Introduction II. Stem Cell Differentiation into Platelets III. Isolation and Culture of Megakaryocytes IV. Biochemical Analyses V. Other Plateletlike Reactions in Megakaryocytes VI. Summary References 12. Future Directions in Platelet Research I. Platelet Activation II. Platelet Aggregation III. Platelet Adhesion IV. Physiological Consequences of Platelet Activation V. Platelet Function in Clot Formation VI. Synthesis of Platelet Proteins and the Development of Platelet Structure VII. Diseases Involving Platelets VIII. Summary Index