Molecular And Cellular Biology Of Platelet Formation

This book gives a comprehensive insight into platelet biogenesis, platelet signal transduction, involvement of platelets in disease, the use of diverse animal models for platelet research and future perspectives in regard to platelet production and gene therapy. Being written by international experts, the book is a concise state-of-the art work in the field of platelet biogenesis, biology and research. It represents an indispensable tool for research scientists in biomedicine, vascular biology, hematopoiesis and hemostasis and specifically for scientists in platelet research, as well as for clinicians in the field of hematology and transfusion medicine.​

David Kuter and a host of leading international researchers summarize in one volume all the knowledge of thrombopoietins (TPO) available today. The distinguished experts review the history of the search to discover TPO, describe the molecular and biological characteristics of this new molecule, and present the results of the preclinical animal experiments that will guide clinical use of this new hormone. Along the way they provide the most recent and comprehensive guide to the biology of megakaryocytes and platelets.

12 The average human body has on the order of 10 circulating platelets. They are crucial for hemostasis, and yet excessive platelet activation is a major cause of m- bidity and mortality in Western societies. It is therefore not surprising that platelets have become one of the most extensively investigated biological cell types. We are, however, far from understanding precisely how platelets become activated under physiological and pathophysiological conditions. In addition, there are large gaps in our knowledge of platelet production from their giant precursor cell, the megakar- cyte. Understanding megakaryocyte biology will be crucial for the development of platelet gene targeting. The aim of Platelets and Megakaryocytes is therefore to bring together established and recently developed techniques to provide a comprehensive guide to the study of both the platelet and the megakaryocyte. It consists of five s- tions split between two volumes. The more functional assays appear in Volume 1, whereas Volume 2 includes signaling techniques, postgenomic methods, and a n- ber of key perspectives chapters. Part I of Volume 1, Platelets and Megakaryocytes: Functional Assays, describes many well-established approaches to the study of platelet function, including aggregometry, secretion, arachidonic acid metabolism, procoagulant responses, pla- let adhesion under static or flow conditions, flow cytometry, and production of microparticles. Although one would ideally wish to perform experiments with human platelets, studies within the circulation using intravital microscopy require the use of animal models, which are described in Chapter 16, vol. 1.

The main aim of this fourth volume is to complement the first three volumes published in 2004 and 2012 by adding advanced methodologies and perspectives. Chapters guide readers through new techniques into the study of platelets and megakaryocytes, including new imaging approaches, new methods for platelet production in vitro, and systems biology approaches. Written in the highly successful Methods in Molecular Biology series format, methods chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and vital tips on troubleshooting or avoiding known pitfalls. Authoritative and up-to-date, Platelets and Megakaryocytes: Volume 4, Additional Protocols and Perspectives adds a wealth of new expertise for the labs of scientists working in this key biological area of study.

New techniques to study cell signaling and function can develop at a staggering pace; however, many approaches are as valid today as on the day they were established. Thus, the main aim of Platelets and Megakaryocytes: Volume 3, Additional Protocols and Perspectives is to complement the first two volumes published in 2004 by adding recently developed state of the art techniques. Conveniently divided into three sections, this detailed volume covers techniques to study platelet function, approaches to investigate megakaryocyte function, and perspectives on important overall concepts in the field of megakaryocyte and platelet biology. Written in the highly successful Methods in Molecular BiologyTM series format, methods chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and vital tips on troubleshooting and avoiding known pitfalls. Authoritative and up-to-date, Platelets and Megakaryocytes: Volume 3, Additional Protocols and Perspectives adds a wealth of new expertise for the labs of scientists working in this key biological area of study.

For both volumes: A comprehensive collection of cutting-edge methods for the molecular and cellular analysis of platelets and megakaryocytes. Volume 1 details basic and advanced techniques for analyzing platelet and megakaryocyte function. The approaches presented for platelet analysis include aggregometry, secretion, arachidonic acid metabolism, procoagulent response, platelet adhesion under static and flow conditions, flow cytometry, and production of microparticles. The techniques for study of megakaryocyte function allow the measurement of specialized structures for platelet production, the appearance of platelet-specific surface receptors, and the increase in ploidy. Volume 2 offers techniques for studying many aspects of signaling in platelets and megakaryocytes, as well as state-of-the-art commentaries on our understanding of these cells. The methods include ligand-binding assays, the study of protein and lipid kinases and phosphatases, the analysis of lipid rafts, and the measurement of intracellular calcium levels. There are also techniques for study of electrophysiological events, nitric oxide signaling, venom proteins, and for the internalization of proteins into platelets through permeabilization. This volume also describes the application of molecular and post-genomic methods for the study of platelets and megakaryocytes. All protocols follow the successful Methods in Molecular Biology⢠series format, each one offering step-by-step laboratory instructions, an introduction outlining the principle behind the technique, lists of equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. The two volumes offer novice and experienced cell biologists, hematologists, and clinicians not only a benchmark survey of the field, but also a comprehensive library of proven techniques essential for productive research on platelets and megakaryocytes today.

'Provides comprehensive detail on the various aspects of particular molecules involved in the phases of injury and repair and the cellular movements and processes....This is an excellent reference book for libraries serving biology and health science clientele and for workers in this field of research.' -American Scientist, from a review of the First Edition All chapters of this second edition have been completely revised and expanded-especially the chapters on growth factors and extracellular matrix molecules. New chapters discuss provisional matrix proteins, extracellular matrix receptors, and scarring versus nonscarring wound healing.

Platelets have been an important model system in which to study various aspects of signal transduction. In spite of the fact that platelets are anucleated cells, it has been possible to assess the relationship between receptors, transducers and effectors, and specific platelet physiological responses. As a consequence, discrete biochemical events can be related to shape change, aggregation, and secretion. In addition to undergoing these internal biochemical changes, activated platelets express glycoproteins receptors for adhesive proteins on their surfaces; these help consolidation of the initial platelet aggregate to stop bleeding and start repair. When this protective action of platelets is exaggerated, a pathological situation arises. Abnormal platelet function is associated with thrombosis, atherosclerosis, and bleeding disorders. This book deals with the most important aspects of platelet signal transduction that have been revealed in the past few years. Emphasis is given to knowledge gained in the area of glycoprotein receptors or integrins that bind adhesive proteins and play a crucial role in thrombosis. One of these integrins also serves as a collagen receptor on platelets. Collagen and thrombin are primary activators at sites of vascular injury. The main thrombin receptor recently was recognized as a seven trans-membrane domain receptor, and attention is now focused on the development of thrombin receptor antagonists that might prove to be useful in treatment of thrombosis and restenosis. The formation and release of thromboxane A2 n activated platelets help to recruit additional platelets to the injury site; the receptor for thromboxane A2 is a newly discovered seven trans-membrane domain receptor that is also covered in this book. The coupling of platelet receptors to the effectors or second-messenger-producting enzymes is mostly through heterotrimeric and low molecular weight GTP-binding proteins, which have an important role in the stimulation or inhibition of platelet effectors. Two chapters deal with the role of GTP-binding proteins in human platelets. Several chapters are devoted to the effectors, including phospholipases C, A2, D, and phosphatidylinositol 3-kinase; the mobilization of Ca2+; and the formation of cAMP, cGMP, nitric oxide, and the role of the NA+/K+ exchanger. This is integrated with information on the activation of important protein kinases - that is, protein kinase C, Ca2+ -calmodulin-dependent protein kinases, cAMP and cGMP-dependent kinases, and tyrosine kinases - and on how these activities lead to changes in platelet cytoskeleton to cause shape change, aggregation, and secretion.