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Nitric Oxide in Health and Disease
Book Reviews Immune Effector Mechanisms in Parasitic Infections edited by F.Y. Liew and K. Vickerman, Philosophical Transactions of the Royal Society of London Series B, Vol. 352, No. 1359, 1997. pp 1293–1394, ISSN 0962–8436 It is over ten years since the Royal Society last held a discussion meeting concerned with the immunology of parasitic diseases and, since then, the whole field has changed almost beyond recognition. These changes are reflected in the 12 contributions, by a total of 47 authors all from internationally recognized groups, mainly British and American, to this meeting held in February 1997. The most significant change has been the integration of the concepts and techniques of molecular biology and immunology into the domain of parasitology, resulting in a much clearer understanding of the ways that parasites survive in immunologically hostile hosts, the mechanisms whereby they are destroyed and the implications for possible immunological intervention. Central to our understanding of these processes is the unravelling of the diverse roles of cytokines, particularly with respect to the ways they reflect the Th1/Th2 dichotomy, and the functions of the apparently omnipresent effector molecule, nitric oxide (NO). These themes weave their way throughout this volume. The mechanisms of immune evasion dominate the contributions on the survival of mycobacteria in macrophages,
innate immunity to Toxoplasma and antigenic variation in Giardia and are also considered in the paper on pre-erythrocytic immunity in malaria. The roles of cytokines are also discussed in three of these papers and, in more detail, in sections on cytokines and NO, back-signalling from T cells to antigen-presenting cells, protective immunity to intestinal nematodes and morbidity in malaria. This last paper is of particular significance. Any subject can be judged to have reached maturity when findings in the laboratory are translated to the real world; it is particularly gratifying that this paper on morbidity in malaria, as well as ones on genetic susceptibility to leishmanial and mycobacterial infections in Brazil and host–parasite co-evolution in malaria, are concerned with human infections. The message that comes across loud and clear is that laboratory studies are relevant to human disease, and that information so gleaned can be applied to human situations. The possible applications of laboratory studies are also considered by the authors of chapters on gene expression in Toxoplasma and antigenic variation in Giardia and there are pointers to possible future directions. It is also interesting to
Nitric Oxide in Health and Disease by Jill Lincoln, Charles H.V. Hoyle and Geoffrey Burnstock, Cambridge University Press, 1997. £24.95 (pbk) / £70.00 (hbk) (xiv + 363 pages) ISBN 0 521 55977 4 / 0 521 55038 6 The discovery that nitric oxide (NO) is produced by mammalian cells and can serve both as a physiological messenger as well as an effector molecule of immune defense occurred only about a decade ago, but this little molecule has been the subject of intense investigation since that time. The resultant, rapidly developing understanding of the functional role of NO has derived from, and impacted upon, many fields of biological research. In this book, the authors have made an effort to integrate information on NO function from three major areas: regulation of vascular dilation, immunocytotoxicity, and neuronal signaling. As the authors point out, critical insights into the biological activity of NO have come from studies in each of these areas, and it may be a mistake for those of us interested in parasitic systems to consider any one of them in isolation. Malaria is a good example of a disease in which NO has been 504
postulated to have both parasiticidal and neurological effects. The book begins with a review of the synthesis and properties of NO, and of the activity and regulation of the three different isoforms of the nitric oxide synthase enzyme which produce it. It moves rapidly into a discussion of the function of NO in the nervous, vasculatory and immune systems. Intrigued by the seeming paradoxes that NO is both cytotoxic and yet involved in normal physiological processes, as well as both highly and randomly reactive, yet unexpectedly predictable in its physiological activity, the authors concentrate an entire section on the potential ‘dark side’ of the molecule with a comprehensive review of its pathological implications. They make no assumption that the reader will have much prior exposure to the NO literature, and thus take pains to begin each section with a basic overview, in an easy-to-follow,
0169-4758/98/$ – see front matter © 1998 Elsevier Science. All rights reserved.
note that the traditional division between eukaryote and prokaryote microparasites is breaking down and that it is now recognized that there is much in common between the immune responses and parasite killing in hosts infected with intracellular parasitic protozoa and with mycobacteria. It is evident from this volume that lessons learned from one organism can be applied to others and, in this context, the significance of biochemical and molecular features common to a number of parasites is also becoming apparent as exemplified by a paper on the surface molecules of trypanosomatid flagellates and which is also alluded to elsewhere. All the chapters in this volume are readable and authoritative with up-to-date references, so they are likely to be a good source of information for some years to come. I recommend this book to researchers, lecturers and students, not only those involved in parasitology but also immunologists concerned with infectious diseases. As it is published in a stand-alone form, this volume should be available even to those not fortunate to have The Philosophical Transactions in their own libraries. Frank Cox Department of Infectious and Tropical Diseases London School of Hygiene and Tropical Medicine Keppel Street London UK WCIE 7HT
almost conversational, style. In addition, they take care to point out areas in which questions remain and more research is needed. In this aspect, the book differs from more specialized references such as collections of reports from symposia. The book ends with an overview of experimental approaches to the study of the biological function of NO, and a detailed listing of protocols for its quantitation and localization. This reference will be useful for those scientists who wish to explore the possibility that NO plays a role in the disease in which they are interested, and are looking for a ‘one-stop shopping’ collection of ideas and protocols to get them started. Even in the case of those who are already knowledgeable about NO, it may aid in broadening their thinking about its potential physiological and pathological effects in the system they are studying. Stephanie L. James Parasitology and International Health Branch NIAID, National Institutes of Health Solar Building Room 3A-02 Bethesda MD 20892, USA
Parasitology Today, vol. 14, no. 12, 1998
innate immunity to Toxoplasma and antigenic variation in Giardia and are also considered in the paper on pre-erythrocytic immunity in malaria. The roles of cytokines are also discussed in three of these papers and, in more detail, in sections on cytokines and NO, back-signalling from T cells to antigen-presenting cells, protective immunity to intestinal nematodes and morbidity in malaria. This last paper is of particular significance. Any subject can be judged to have reached maturity when findings in the laboratory are translated to the real world; it is particularly gratifying that this paper on morbidity in malaria, as well as ones on genetic susceptibility to leishmanial and mycobacterial infections in Brazil and host–parasite co-evolution in malaria, are concerned with human infections. The message that comes across loud and clear is that laboratory studies are relevant to human disease, and that information so gleaned can be applied to human situations. The possible applications of laboratory studies are also considered by the authors of chapters on gene expression in Toxoplasma and antigenic variation in Giardia and there are pointers to possible future directions. It is also interesting to
Nitric Oxide in Health and Disease by Jill Lincoln, Charles H.V. Hoyle and Geoffrey Burnstock, Cambridge University Press, 1997. £24.95 (pbk) / £70.00 (hbk) (xiv + 363 pages) ISBN 0 521 55977 4 / 0 521 55038 6 The discovery that nitric oxide (NO) is produced by mammalian cells and can serve both as a physiological messenger as well as an effector molecule of immune defense occurred only about a decade ago, but this little molecule has been the subject of intense investigation since that time. The resultant, rapidly developing understanding of the functional role of NO has derived from, and impacted upon, many fields of biological research. In this book, the authors have made an effort to integrate information on NO function from three major areas: regulation of vascular dilation, immunocytotoxicity, and neuronal signaling. As the authors point out, critical insights into the biological activity of NO have come from studies in each of these areas, and it may be a mistake for those of us interested in parasitic systems to consider any one of them in isolation. Malaria is a good example of a disease in which NO has been 504
postulated to have both parasiticidal and neurological effects. The book begins with a review of the synthesis and properties of NO, and of the activity and regulation of the three different isoforms of the nitric oxide synthase enzyme which produce it. It moves rapidly into a discussion of the function of NO in the nervous, vasculatory and immune systems. Intrigued by the seeming paradoxes that NO is both cytotoxic and yet involved in normal physiological processes, as well as both highly and randomly reactive, yet unexpectedly predictable in its physiological activity, the authors concentrate an entire section on the potential ‘dark side’ of the molecule with a comprehensive review of its pathological implications. They make no assumption that the reader will have much prior exposure to the NO literature, and thus take pains to begin each section with a basic overview, in an easy-to-follow,
0169-4758/98/$ – see front matter © 1998 Elsevier Science. All rights reserved.
note that the traditional division between eukaryote and prokaryote microparasites is breaking down and that it is now recognized that there is much in common between the immune responses and parasite killing in hosts infected with intracellular parasitic protozoa and with mycobacteria. It is evident from this volume that lessons learned from one organism can be applied to others and, in this context, the significance of biochemical and molecular features common to a number of parasites is also becoming apparent as exemplified by a paper on the surface molecules of trypanosomatid flagellates and which is also alluded to elsewhere. All the chapters in this volume are readable and authoritative with up-to-date references, so they are likely to be a good source of information for some years to come. I recommend this book to researchers, lecturers and students, not only those involved in parasitology but also immunologists concerned with infectious diseases. As it is published in a stand-alone form, this volume should be available even to those not fortunate to have The Philosophical Transactions in their own libraries. Frank Cox Department of Infectious and Tropical Diseases London School of Hygiene and Tropical Medicine Keppel Street London UK WCIE 7HT
almost conversational, style. In addition, they take care to point out areas in which questions remain and more research is needed. In this aspect, the book differs from more specialized references such as collections of reports from symposia. The book ends with an overview of experimental approaches to the study of the biological function of NO, and a detailed listing of protocols for its quantitation and localization. This reference will be useful for those scientists who wish to explore the possibility that NO plays a role in the disease in which they are interested, and are looking for a ‘one-stop shopping’ collection of ideas and protocols to get them started. Even in the case of those who are already knowledgeable about NO, it may aid in broadening their thinking about its potential physiological and pathological effects in the system they are studying. Stephanie L. James Parasitology and International Health Branch NIAID, National Institutes of Health Solar Building Room 3A-02 Bethesda MD 20892, USA
Parasitology Today, vol. 14, no. 12, 1998