This series of books, devoted to aspects of blood cell biochemistry, development, immu­ nology, and ultrastructure, has evolved and separated from the long-established Plenum series Subcellular Biochemistry. It is the intention of these volumes to draw together related areas of investigation and to provide, in the fullness of time, complete coverage of this rapidly advancing important biomedical discipline. Both fundamental and medically applied topics, dealing with normal and pathological cells, will be included. This, the first volume of the series, contains a diverse collection of chapters, all of which relate to erythroid cells. The range of material included is extremely broad and the authors have used contrasting technical approaches, both within their personal experimen­ tal studies and within their manuscripts. This has led to the production of a very interest­ ing compilation, which does, nevertheless, possess a strong overall thematic unity. As with all edited volumes, some topics of importance and interest are not included. This may be because of oversight on my part, as editor, or because the authors originally selected failed to submit their manuscript by the agreed-upon submission date. For these omissions I take full responsibility and trust that at least some of the topics omitted, for instance membrane cation transport systems, will be covered within a future volume of the series. This book commences with two chapters of a developmental nature.

Blood Cell Biochemistry was initially conceived as part of the Plenum series Subcellular Biochemistry, from which it has developed into a separate series. The present volume is devoted primarily to contributions on megakaryocytes and platelets and, to a lesser extent, to macrophages and eosinophils. The book does not attempt a rigorous or total coverage of the particular topics; it represents the areas of current scientific activity and interest that were selected by the editor at the commencement of this project. In general, the approach has been similar to that adopted for Volume 1 of the series (Erythroid Cells); the same approach will be followed subsequently in Volume 3 (Lymphocytes and Granulocytes). This book opens with a developmentally oriented chapter by Janine Breton-Gorius on megakaryocyte maturation and platelet release in normal conditions, which serves to set the scene ultrastructurally for much of the data that follow. The biosynthesis and process- ing of platelet glycoproteins in megakaryocytes is dealt with by Alain Duperray and his colleagues, and thereby provides an in-depth biochemical survey of the megakaryocyte.The applications and strengths of crossed immunoelectrophoresis for the study of platelet membrane proteins is then covered by Simon Karpatkin, and a detailed account of the heredity disorders of platelet function is provided by Francine Rendu and Evelyne Dupuy.

Basophils and mast cells are similar but unique secretory cells with a well-documented role in immediate-hypersensitivity reactions. The presence of these cells in various cell­ mediated hypersensitivity reactions, in tissues of multiple diseases, and as a component of the host reaction to injury and repair in numerous circumstances is well known. Release of stored and newly generated mediators of inflammation from basophils and mast cells contributes to the cascade of pathogenetic events in circumstances under which these release reactions occur. Despite insights acquired through studies of these pathologic events, the role of basophils and mast cells and their secretory products in health is not known. In this book, I review much of the structural information regarding basophils and mast cells of multiple species. Ultrastructural studies of rat mast cells historically precede and quantitatively exceed similar studies of basophils and mast cells of other species. Therefore, I first review these background studies as an entity. Then I discuss the contents of two prominent organelles-granules and lipid bodies-in basophils and mast cells of several species. The ultrastructural morphology of basophils and mast cells in three species is presented in detail to establish appropriate guidelines for their recognition and to provide general rules for analysis which are appropriate for the identification of these cells in other species as well.

To produce a comprehensive overview of macrophages and related cell types in a short review volume is an impossible task. When I selected the topics to be included, some equally important areas were omitted by necessity, and for this I apologize. My choices have been somewhat eclectic, touching subjects of personal interest (such as osteoclast biology and macrophage electrophysiology) or of current fashion (apopto­ sis, antigen processing, cell adhesion molecules). The book has also had to encompass areas of a more general flavor to provide balance for the general reader (such as reviews of macrophage development, heterogeneity, and function, and of the surface molecules expressed by macrophages). I thank all the authors for their prompt sub­ missions; all have been of high quality, and my editorial tasks, thankfully, have been minimal. Michael A. Horton London, United Kingdom ix Contents Chapter J An Overview of Receptors of MPS Cells lain Fraser and Siam on Gordon 1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. The Mononuclear Phagocyte System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 3. Diversity of Macrophage Plasma Membrane Receptors. . . . . . . . . . . . . . . . 6 3. 1 A Structural Approach to Classification . . . . . . . . . . . . . . . . . . . . . . . . . . 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3. 2 Multisubunit Receptors 3. 3 Soluble Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3. 4 Lectins and Lectin-Like Receptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 4. Functions and Selected Examples. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . 14 4. 1 Growth, Differentiation, and Modulation . . . . . . . . . . . . . . . . . . . . . . . . 14 4. 2 Cell-Cell and Cell-Matrix Interactions. . . . . . . . . . . . . . . . . . . . . . . . . . . 16 4. 3 Endocytosis and Scavenger Receptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 4. 4 Secretory Responses and Biosynthesis of Effector Molecules . . . . . . 17 5. Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 6. References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 . . . . . . . . . . . . . . . . . . . .

The science of blood groups was born at the beginning of this century, when the field of immunology married that of genetics. Most of the subsequent progress in immunogenetics was achieved by British investigators. The six consecutive editions of the unequaled Blood Groups in Man have long been considered as the bible of blood groupers. It is quite unfortunate that this book has not been revisited since 1975. Although one cannot do without immunogenetics, which remains useful for the identification of new blood groups and genetic studies, the focus of interest has moved somewhat today. After several decades, the molecular basis of blood groups can be investigated by biochemists. From 1950 to 1980, the ABO, Hh, and Lewis blood groups served as models and their chemical basis came to be established. The red cell membrane glycophorins carrying the MN and Ss antigens and the glycolipids with P blood group specificities were also identified and characterized. The chemical basis of the other groups, however, remained largely unknown.

Historically, the field of hematopoietic growth factor research began with the work of Carnot and Deflandre-in 1906 they suggested that the rate of erythropoiesis is regulated by a humoral factor found in the blood, namely, erythropoietin. From this comparatively early start, accelerating progress has been made in erythropoietin research, which demon­ strates the general trends in this field of study. Erythropoietin was purified to homogeneity by 1977 (from enormous quantities of urine from aplastic anemia patients). Subsequently, the gene for erythropoietin has been cloned (1985), and massive quantities of this growth factor have been produced for clinical trials (late 1980s onward). Erythropoietin has become established as a pharmaceutical product of great value in the treatment of a number of diseases, most notably chronic renal failure. Once the ligand had been cloned, interest turned to the erythropoietin receptor, which was cloned in 1989. Since then, structure/ function studies have been performed on receptor mutants, cellular signaling events down­ stream from the occupied receptor have been identified, and the specific producer cell types and molecular stimuli for erythropoietin production have been thoroughly investigated, as has the regulation of erythropoietin gene transcription. This schedule of events since the 1970s typifies that seen for a number of hematopoietic growth factors. Along the way, the hematopoietic growth factors have been recognized as members of the cytokine family of signaling molecules that are important in a number of different physiological and patholog­ ical situations (see below).

Since the first concepts of gene therapy were formulated, the hemopoietic system has been considered the most natural first target tissue for genetic manipulation. The reasons for this include the fact that a very large number of inherited disorders (including some of the most common disorders, such as the hemoglobinopathies) are disorders of the hemopoietic system, and the large amount of experience in hematopoietic transplantation biology. The consequence of this resulted in the first clinical trial of gene therapy in 1989, where two children suffering from severe combined immune deficiency (ADA-SCID) were transplanted with T-cells express­ ing adenosine deaminase (the defective enzyme in patients with this disorder). The partial success of this treatment was perhaps responsible for undue optimism among those proposing other gene therapy treatments within the hematopoietic system, and it has since become clear that there are a number of technical and biological difficulties to overcome before hematopoietic gene therapy becomes a mainstream therapeutic strategy. The chapters in this book evaluate the need for gene therapy in the hematopoietic system, discuss how efficient gene transfer and expression can be achieved in the target cells, highlight areas of difficulty to be addressed, and examine a number of potential applications of the gene therapy approach. The book begins with a chapter by Testa and colleagues, discussing the various sources of hematopoietic cells for both transplantation and gene therapy.

This, the third volume of the Blood Cell Biochemistry series, follows the pattern estab- lished in the two previous volumes by containing up-to-date specialist reviews of topics of current interest within the field of study defined by the subtitle. Thus, the topics included can be loosely classified under the broad subtitle "Lymphocytes and Granulocytes," but this does not indicate the full scope of content, scientific interest, and emphasis of the present volume. The opening chapter, by Antonio Bonati, surveys the currently available bio- chemical, immunological, and molecular markers of hemopoietic precursor cells. This is followed, appropriately, by a contribution from Arnold S. Freedman on the cell surface markers in leukemia and lymphoma. In a detailed chapter, Annette Schmitt-Graff and Giulio Gabbiani discuss the cytoskeletal organization of normal and leukemic lympho- cytes and lymphoblasts. John C. Cambier and his colleagues then present a discussion of the signaling events in T-Iymphocyte-dependent B-Iymphocyte activation.Lymphocyte IgE receptors and IgE-binding factors are dealt with by Kwang-Myong Kim and his colleagues, and the role ofgranule mediators in lymphocyte-mediated cytolysis is covered by John Ding-E Young and his associates. A short contribution from James D. Katz deals with the intricacies and difficulties of studies on the complement C3b (CRl) receptor and its cytoskeletal interactions in neutrophils. Arthur K. Sullivan then presents an in-depth survey of the membrane biochemistry surrounding the flow of granule organelles in leukocyte differentiation.

Since the first concepts of gene therapy were formulated, the hemopoietic system has been considered the most natural first target tissue for genetic manipulation. The reasons for this include the fact that a very large number of inherited disorders (including some of the most common disorders, such as the hemoglobinopathies) are disorders of the hemopoietic system, and the large amount of experience in hematopoietic transplantation biology. The consequence of this resulted in the first clinical trial of gene therapy in 1989, where two children suffering from severe combined immune deficiency (ADA-SCID) were transplanted with T-cells express­ ing adenosine deaminase (the defective enzyme in patients with this disorder). The partial success of this treatment was perhaps responsible for undue optimism among those proposing other gene therapy treatments within the hematopoietic system, and it has since become clear that there are a number of technical and biological difficulties to overcome before hematopoietic gene therapy becomes a mainstream therapeutic strategy. The chapters in this book evaluate the need for gene therapy in the hematopoietic system, discuss how efficient gene transfer and expression can be achieved in the target cells, highlight areas of difficulty to be addressed, and examine a number of potential applications of the gene therapy approach. The book begins with a chapter by Testa and colleagues, discussing the various sources of hematopoietic cells for both transplantation and gene therapy.

Historically, the field of hematopoietic growth factor research began with the work of Carnot and Deflandre-in 1906 they suggested that the rate of erythropoiesis is regulated by a humoral factor found in the blood, namely, erythropoietin. From this comparatively early start, accelerating progress has been made in erythropoietin research, which demon­ strates the general trends in this field of study. Erythropoietin was purified to homogeneity by 1977 (from enormous quantities of urine from aplastic anemia patients). Subsequently, the gene for erythropoietin has been cloned (1985), and massive quantities of this growth factor have been produced for clinical trials (late 1980s onward). Erythropoietin has become established as a pharmaceutical product of great value in the treatment of a number of diseases, most notably chronic renal failure. Once the ligand had been cloned, interest turned to the erythropoietin receptor, which was cloned in 1989. Since then, structure/ function studies have been performed on receptor mutants, cellular signaling events down­ stream from the occupied receptor have been identified, and the specific producer cell types and molecular stimuli for erythropoietin production have been thoroughly investigated, as has the regulation of erythropoietin gene transcription. This schedule of events since the 1970s typifies that seen for a number of hematopoietic growth factors. Along the way, the hematopoietic growth factors have been recognized as members of the cytokine family of signaling molecules that are important in a number of different physiological and patholog­ ical situations (see below).

Basophils and mast cells are similar but unique secretory cells with a well-documented role in immediate-hypersensitivity reactions. The presence of these cells in various cell­ mediated hypersensitivity reactions, in tissues of multiple diseases, and as a component of the host reaction to injury and repair in numerous circumstances is well known. Release of stored and newly generated mediators of inflammation from basophils and mast cells contributes to the cascade of pathogenetic events in circumstances under which these release reactions occur. Despite insights acquired through studies of these pathologic events, the role of basophils and mast cells and their secretory products in health is not known. In this book, I review much of the structural information regarding basophils and mast cells of multiple species. Ultrastructural studies of rat mast cells historically precede and quantitatively exceed similar studies of basophils and mast cells of other species. Therefore, I first review these background studies as an entity. Then I discuss the contents of two prominent organelles-granules and lipid bodies-in basophils and mast cells of several species. The ultrastructural morphology of basophils and mast cells in three species is presented in detail to establish appropriate guidelines for their recognition and to provide general rules for analysis which are appropriate for the identification of these cells in other species as well.

This series of books, devoted to aspects of blood cell biochemistry, development, immu­ nology, and ultrastructure, has evolved and separated from the long-established Plenum series Subcellular Biochemistry. It is the intention of these volumes to draw together related areas of investigation and to provide, in the fullness of time, complete coverage of this rapidly advancing important biomedical discipline. Both fundamental and medically applied topics, dealing with normal and pathological cells, will be included. This, the first volume of the series, contains a diverse collection of chapters, all of which relate to erythroid cells. The range of material included is extremely broad and the authors have used contrasting technical approaches, both within their personal experimen­ tal studies and within their manuscripts. This has led to the production of a very interest­ ing compilation, which does, nevertheless, possess a strong overall thematic unity. As with all edited volumes, some topics of importance and interest are not included. This may be because of oversight on my part, as editor, or because the authors originally selected failed to submit their manuscript by the agreed-upon submission date. For these omissions I take full responsibility and trust that at least some of the topics omitted, for instance membrane cation transport systems, will be covered within a future volume of the series. This book commences with two chapters of a developmental nature.

Blood Cell Biochemistry was initially conceived as part of the Plenum series Subcellular Biochemistry, from which it has developed into a separate series. The present volume is devoted primarily to contributions on megakaryocytes and platelets and, to a lesser extent, to macrophages and eosinophils. The book does not attempt a rigorous or total coverage of the particular topics; it represents the areas of current scientific activity and interest that were selected by the editor at the commencement of this project. In general, the approach has been similar to that adopted for Volume 1 of the series (Erythroid Cells); the same approach will be followed subsequently in Volume 3 (Lymphocytes and Granulocytes). This book opens with a developmentally oriented chapter by Janine Breton-Gorius on megakaryocyte maturation and platelet release in normal conditions, which serves to set the scene ultrastructurally for much of the data that follow. The biosynthesis and process- ing of platelet glycoproteins in megakaryocytes is dealt with by Alain Duperray and his colleagues, and thereby provides an in-depth biochemical survey of the megakaryocyte.The applications and strengths of crossed immunoelectrophoresis for the study of platelet membrane proteins is then covered by Simon Karpatkin, and a detailed account of the heredity disorders of platelet function is provided by Francine Rendu and Evelyne Dupuy.

This series of books, devoted to aspects of blood cell biochemistry, development, immu­ nology, and ultrastructure, has evolved and separated from the long-established Plenum series Subcellular Biochemistry. It is the intention of these volumes to draw together related areas of investigation and to provide, in the fullness of time, complete coverage of this rapidly advancing important biomedical discipline. Both fundamental and medically applied topics, dealing with normal and pathological cells, will be included. This, the first volume of the series, contains a diverse collection of chapters, all of which relate to erythroid cells. The range of material included is extremely broad and the authors have used contrasting technical approaches, both within their personal experimen­ tal studies and within their manuscripts. This has led to the production of a very interest­ ing compilation, which does, nevertheless, possess a strong overall thematic unity. As with all edited volumes, some topics of importance and interest are not included. This may be because of oversight on my part, as editor, or because the authors originally selected failed to submit their manuscript by the agreed-upon submission date. For these omissions I take full responsibility and trust that at least some of the topics omitted, for instance membrane cation transport systems, will be covered within a future volume of the series. This book commences with two chapters of a developmental nature.

Blood Cell Biochemistry was initially conceived as part of the Plenum series Subcellular Biochemistry, from which it has developed into a separate series. The present volume is devoted primarily to contributions on megakaryocytes and platelets and, to a lesser extent, to macrophages and eosinophils. The book does not attempt a rigorous or total coverage of the particular topics; it represents the areas of current scientific activity and interest that were selected by the editor at the commencement of this project. In general, the approach has been similar to that adopted for Volume 1 of the series (Erythroid Cells); the same approach will be followed subsequently in Volume 3 (Lymphocytes and Granulocytes). This book opens with a developmentally oriented chapter by Janine Breton-Gorius on megakaryocyte maturation and platelet release in normal conditions, which serves to set the scene ultrastructurally for much of the data that follow. The biosynthesis and process- ing of platelet glycoproteins in megakaryocytes is dealt with by Alain Duperray and his colleagues, and thereby provides an in-depth biochemical survey of the megakaryocyte.The applications and strengths of crossed immunoelectrophoresis for the study of platelet membrane proteins is then covered by Simon Karpatkin, and a detailed account of the heredity disorders of platelet function is provided by Francine Rendu and Evelyne Dupuy.

Basophils and mast cells are similar but unique secretory cells with a well-documented role in immediate-hypersensitivity reactions. The presence of these cells in various cell­ mediated hypersensitivity reactions, in tissues of multiple diseases, and as a component of the host reaction to injury and repair in numerous circumstances is well known. Release of stored and newly generated mediators of inflammation from basophils and mast cells contributes to the cascade of pathogenetic events in circumstances under which these release reactions occur. Despite insights acquired through studies of these pathologic events, the role of basophils and mast cells and their secretory products in health is not known. In this book, I review much of the structural information regarding basophils and mast cells of multiple species. Ultrastructural studies of rat mast cells historically precede and quantitatively exceed similar studies of basophils and mast cells of other species. Therefore, I first review these background studies as an entity. Then I discuss the contents of two prominent organelles-granules and lipid bodies-in basophils and mast cells of several species. The ultrastructural morphology of basophils and mast cells in three species is presented in detail to establish appropriate guidelines for their recognition and to provide general rules for analysis which are appropriate for the identification of these cells in other species as well.

To produce a comprehensive overview of macrophages and related cell types in a short review volume is an impossible task. When I selected the topics to be included, some equally important areas were omitted by necessity, and for this I apologize. My choices have been somewhat eclectic, touching subjects of personal interest (such as osteoclast biology and macrophage electrophysiology) or of current fashion (apopto­ sis, antigen processing, cell adhesion molecules). The book has also had to encompass areas of a more general flavor to provide balance for the general reader (such as reviews of macrophage development, heterogeneity, and function, and of the surface molecules expressed by macrophages). I thank all the authors for their prompt sub­ missions; all have been of high quality, and my editorial tasks, thankfully, have been minimal. Michael A. Horton London, United Kingdom ix Contents Chapter J An Overview of Receptors of MPS Cells lain Fraser and Siam on Gordon 1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. The Mononuclear Phagocyte System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 3. Diversity of Macrophage Plasma Membrane Receptors. . . . . . . . . . . . . . . . 6 3. 1 A Structural Approach to Classification . . . . . . . . . . . . . . . . . . . . . . . . . . 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 3. 2 Multisubunit Receptors 3. 3 Soluble Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 3. 4 Lectins and Lectin-Like Receptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 4. Functions and Selected Examples. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . 14 4. 1 Growth, Differentiation, and Modulation . . . . . . . . . . . . . . . . . . . . . . . . 14 4. 2 Cell-Cell and Cell-Matrix Interactions. . . . . . . . . . . . . . . . . . . . . . . . . . . 16 4. 3 Endocytosis and Scavenger Receptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 4. 4 Secretory Responses and Biosynthesis of Effector Molecules . . . . . . 17 5. Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 6. References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 . . . . . . . . . . . . . . . . . . . .

The science of blood groups was born at the beginning of this century, when the field of immunology married that of genetics. Most of the subsequent progress in immunogenetics was achieved by British investigators. The six consecutive editions of the unequaled Blood Groups in Man have long been considered as the bible of blood groupers. It is quite unfortunate that this book has not been revisited since 1975. Although one cannot do without immunogenetics, which remains useful for the identification of new blood groups and genetic studies, the focus of interest has moved somewhat today. After several decades, the molecular basis of blood groups can be investigated by biochemists. From 1950 to 1980, the ABO, Hh, and Lewis blood groups served as models and their chemical basis came to be established. The red cell membrane glycophorins carrying the MN and Ss antigens and the glycolipids with P blood group specificities were also identified and characterized. The chemical basis of the other groups, however, remained largely unknown.

Historically, the field of hematopoietic growth factor research began with the work of Carnot and Deflandre-in 1906 they suggested that the rate of erythropoiesis is regulated by a humoral factor found in the blood, namely, erythropoietin. From this comparatively early start, accelerating progress has been made in erythropoietin research, which demon­ strates the general trends in this field of study. Erythropoietin was purified to homogeneity by 1977 (from enormous quantities of urine from aplastic anemia patients). Subsequently, the gene for erythropoietin has been cloned (1985), and massive quantities of this growth factor have been produced for clinical trials (late 1980s onward). Erythropoietin has become established as a pharmaceutical product of great value in the treatment of a number of diseases, most notably chronic renal failure. Once the ligand had been cloned, interest turned to the erythropoietin receptor, which was cloned in 1989. Since then, structure/ function studies have been performed on receptor mutants, cellular signaling events down­ stream from the occupied receptor have been identified, and the specific producer cell types and molecular stimuli for erythropoietin production have been thoroughly investigated, as has the regulation of erythropoietin gene transcription. This schedule of events since the 1970s typifies that seen for a number of hematopoietic growth factors. Along the way, the hematopoietic growth factors have been recognized as members of the cytokine family of signaling molecules that are important in a number of different physiological and patholog­ ical situations (see below).

Since the first concepts of gene therapy were formulated, the hemopoietic system has been considered the most natural first target tissue for genetic manipulation. The reasons for this include the fact that a very large number of inherited disorders (including some of the most common disorders, such as the hemoglobinopathies) are disorders of the hemopoietic system, and the large amount of experience in hematopoietic transplantation biology. The consequence of this resulted in the first clinical trial of gene therapy in 1989, where two children suffering from severe combined immune deficiency (ADA-SCID) were transplanted with T-cells express­ ing adenosine deaminase (the defective enzyme in patients with this disorder). The partial success of this treatment was perhaps responsible for undue optimism among those proposing other gene therapy treatments within the hematopoietic system, and it has since become clear that there are a number of technical and biological difficulties to overcome before hematopoietic gene therapy becomes a mainstream therapeutic strategy. The chapters in this book evaluate the need for gene therapy in the hematopoietic system, discuss how efficient gene transfer and expression can be achieved in the target cells, highlight areas of difficulty to be addressed, and examine a number of potential applications of the gene therapy approach. The book begins with a chapter by Testa and colleagues, discussing the various sources of hematopoietic cells for both transplantation and gene therapy.

This, the third volume of the Blood Cell Biochemistry series, follows the pattern estab- lished in the two previous volumes by containing up-to-date specialist reviews of topics of current interest within the field of study defined by the subtitle. Thus, the topics included can be loosely classified under the broad subtitle "Lymphocytes and Granulocytes," but this does not indicate the full scope of content, scientific interest, and emphasis of the present volume. The opening chapter, by Antonio Bonati, surveys the currently available bio- chemical, immunological, and molecular markers of hemopoietic precursor cells. This is followed, appropriately, by a contribution from Arnold S. Freedman on the cell surface markers in leukemia and lymphoma. In a detailed chapter, Annette Schmitt-Graff and Giulio Gabbiani discuss the cytoskeletal organization of normal and leukemic lympho- cytes and lymphoblasts. John C. Cambier and his colleagues then present a discussion of the signaling events in T-Iymphocyte-dependent B-Iymphocyte activation.Lymphocyte IgE receptors and IgE-binding factors are dealt with by Kwang-Myong Kim and his colleagues, and the role ofgranule mediators in lymphocyte-mediated cytolysis is covered by John Ding-E Young and his associates. A short contribution from James D. Katz deals with the intricacies and difficulties of studies on the complement C3b (CRl) receptor and its cytoskeletal interactions in neutrophils. Arthur K. Sullivan then presents an in-depth survey of the membrane biochemistry surrounding the flow of granule organelles in leukocyte differentiation.

Since the first concepts of gene therapy were formulated, the hemopoietic system has been considered the most natural first target tissue for genetic manipulation. The reasons for this include the fact that a very large number of inherited disorders (including some of the most common disorders, such as the hemoglobinopathies) are disorders of the hemopoietic system, and the large amount of experience in hematopoietic transplantation biology. The consequence of this resulted in the first clinical trial of gene therapy in 1989, where two children suffering from severe combined immune deficiency (ADA-SCID) were transplanted with T-cells express­ ing adenosine deaminase (the defective enzyme in patients with this disorder). The partial success of this treatment was perhaps responsible for undue optimism among those proposing other gene therapy treatments within the hematopoietic system, and it has since become clear that there are a number of technical and biological difficulties to overcome before hematopoietic gene therapy becomes a mainstream therapeutic strategy. The chapters in this book evaluate the need for gene therapy in the hematopoietic system, discuss how efficient gene transfer and expression can be achieved in the target cells, highlight areas of difficulty to be addressed, and examine a number of potential applications of the gene therapy approach. The book begins with a chapter by Testa and colleagues, discussing the various sources of hematopoietic cells for both transplantation and gene therapy.

Historically, the field of hematopoietic growth factor research began with the work of Carnot and Deflandre-in 1906 they suggested that the rate of erythropoiesis is regulated by a humoral factor found in the blood, namely, erythropoietin. From this comparatively early start, accelerating progress has been made in erythropoietin research, which demon­ strates the general trends in this field of study. Erythropoietin was purified to homogeneity by 1977 (from enormous quantities of urine from aplastic anemia patients). Subsequently, the gene for erythropoietin has been cloned (1985), and massive quantities of this growth factor have been produced for clinical trials (late 1980s onward). Erythropoietin has become established as a pharmaceutical product of great value in the treatment of a number of diseases, most notably chronic renal failure. Once the ligand had been cloned, interest turned to the erythropoietin receptor, which was cloned in 1989. Since then, structure/ function studies have been performed on receptor mutants, cellular signaling events down­ stream from the occupied receptor have been identified, and the specific producer cell types and molecular stimuli for erythropoietin production have been thoroughly investigated, as has the regulation of erythropoietin gene transcription. This schedule of events since the 1970s typifies that seen for a number of hematopoietic growth factors. Along the way, the hematopoietic growth factors have been recognized as members of the cytokine family of signaling molecules that are important in a number of different physiological and patholog­ ical situations (see below).

Basophils and mast cells are similar but unique secretory cells with a well-documented role in immediate-hypersensitivity reactions. The presence of these cells in various cell­ mediated hypersensitivity reactions, in tissues of multiple diseases, and as a component of the host reaction to injury and repair in numerous circumstances is well known. Release of stored and newly generated mediators of inflammation from basophils and mast cells contributes to the cascade of pathogenetic events in circumstances under which these release reactions occur. Despite insights acquired through studies of these pathologic events, the role of basophils and mast cells and their secretory products in health is not known. In this book, I review much of the structural information regarding basophils and mast cells of multiple species. Ultrastructural studies of rat mast cells historically precede and quantitatively exceed similar studies of basophils and mast cells of other species. Therefore, I first review these background studies as an entity. Then I discuss the contents of two prominent organelles-granules and lipid bodies-in basophils and mast cells of several species. The ultrastructural morphology of basophils and mast cells in three species is presented in detail to establish appropriate guidelines for their recognition and to provide general rules for analysis which are appropriate for the identification of these cells in other species as well.

This series of books, devoted to aspects of blood cell biochemistry, development, immu­ nology, and ultrastructure, has evolved and separated from the long-established Plenum series Subcellular Biochemistry. It is the intention of these volumes to draw together related areas of investigation and to provide, in the fullness of time, complete coverage of this rapidly advancing important biomedical discipline. Both fundamental and medically applied topics, dealing with normal and pathological cells, will be included. This, the first volume of the series, contains a diverse collection of chapters, all of which relate to erythroid cells. The range of material included is extremely broad and the authors have used contrasting technical approaches, both within their personal experimen­ tal studies and within their manuscripts. This has led to the production of a very interest­ ing compilation, which does, nevertheless, possess a strong overall thematic unity. As with all edited volumes, some topics of importance and interest are not included. This may be because of oversight on my part, as editor, or because the authors originally selected failed to submit their manuscript by the agreed-upon submission date. For these omissions I take full responsibility and trust that at least some of the topics omitted, for instance membrane cation transport systems, will be covered within a future volume of the series. This book commences with two chapters of a developmental nature.

Blood Cell Biochemistry was initially conceived as part of the Plenum series Subcellular Biochemistry, from which it has developed into a separate series. The present volume is devoted primarily to contributions on megakaryocytes and platelets and, to a lesser extent, to macrophages and eosinophils. The book does not attempt a rigorous or total coverage of the particular topics; it represents the areas of current scientific activity and interest that were selected by the editor at the commencement of this project. In general, the approach has been similar to that adopted for Volume 1 of the series (Erythroid Cells); the same approach will be followed subsequently in Volume 3 (Lymphocytes and Granulocytes). This book opens with a developmentally oriented chapter by Janine Breton-Gorius on megakaryocyte maturation and platelet release in normal conditions, which serves to set the scene ultrastructurally for much of the data that follow. The biosynthesis and process- ing of platelet glycoproteins in megakaryocytes is dealt with by Alain Duperray and his colleagues, and thereby provides an in-depth biochemical survey of the megakaryocyte.The applications and strengths of crossed immunoelectrophoresis for the study of platelet membrane proteins is then covered by Simon Karpatkin, and a detailed account of the heredity disorders of platelet function is provided by Francine Rendu and Evelyne Dupuy.