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Apoptosis and Autoimmunity - From Mechanisms to Treatments - J. Kalden, M. Herrmann (Wiley-VCH, 2003) WW PDF

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Apoptosis and Autoimmunity Edited by M. Herrmann and J.R. Kalden Apoptosis and Autoimmunity. From Mechanisms to Treatments. Edited by J.R. Kalden, M. Herrmann Copyright © 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30442-8 Further titles of interest Stuhler, G. / Walden, P. (Eds.) Cancer Immune Therapy Current and Future Strategies 2000, ISBN 3-527-30441-X Stewart, C.C. / Nicholson, J.K.A. (Eds.) Immunophenotyping Cytometric Cellular Analysis 2000, ISBN 0-471-23957-7 Freshney, R.I. Culture of Animal Cells A Manual of Basic Technique 2000, ISBN 0-471-34889-9 Krauss, G. / Cooper, B.L. / Schönbrunner, N. Biochemistry of Signal Transduction and Regulation Building Blocks and Fine Chemicals 2001, ISBN 3-527-30378-2 Edited by M. Herrmann and J.R. Kalden Apoptosis and Autoimmunity Prof. Dr. Dr. Joachim R. Kalden University of Erlangen-Nuremberg Department of Internal Medicine III and Institute for Clinical Immunology Krankenhausstraße 12 91054 Erlangen, Germany Dr. Dr. Martin Herrmann University of Erlangen-Nuremberg Institute for Clinical Immunology Krankenhausstraße 12 91054 Erlangen, Germany Library of Congress Card No.: applied for British Library Cataloguing-in-Publication Data: A catalogue record for this book is available from the British Library. Bibliographic information published by Die Deutsche Bibliothek Die Deutsche Bibliothek lists this publication in the Deutsche Nationalbibliografie; detailed biblio- graphic data is available in the Internet at <http://dnb.ddb.de>. © 2003 WILEY-VCH Verlag GmbH & Co. KGaG, Weinheim All rights reserved (including those of translation in other languages). No part of this book may be reproduced in any form – nor transmitted or translated into a machine language without writ- ten permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law. Printed in the Federal Republic of Germany Printed on acid-free paper Composition K+V Fotosatz GmbH, Beerfelden Printing betz-druck gmbh, Darmstadt Bookbinding Großbuchbinderei J. Schäffer GmbH & Co. KG, Grünstadt ISBN 3-527-30442-8 � This book was carefully produced. Nevertheless, authors, editors and publisher do not warrant the information contained therein to be free of er- rors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate. More than 100 years ago Paul Ehrlich coined the expression ‘horror autotoxicus’ implicating the existence of autoimmune diseases. After the first description of an autoimmune disease of the thyroid, it soon became obvious that autoimmunity in principle is a self-limiting process, which in certain situations might proceed in an autoaggressive disease situation, when stringent control mechanisms have failed or are dysregulated. Despite of extensive research activities over the past de- cades, the etiology of autoimmune diseases is still enigmatic. Different hypoth- eses have been postulated, although these only partially explain the phenomenon of ‘autoimmunity’. More recently, the relationship between autoimmunity and apoptosis has been the focus of much research activity. Apoptosis as a genetically predetermined pro- cess is not only a vital mechanism sustaining homeostasis in the regulation of im- mune reactivity, but, in addition to being an important factor in general cell phy- siology, produces pronounced morphological changes of cells and the breakdown of cellular constituents by nucleolytic and proteolytic cleavage, resulting in the persisting presence of potential autoantigens. This book presents an up-to-date discussion on apoptosis and its role in autoimmunity. We would like to express our appreciation and gratitude to the authors for their outstanding contributions and cooperation. We also gratefully acknowledge the continuous support of Andreas Sendtko and his colleagues at Wiley-VCH in the realization of this book. Erlangen, July 2002 Martin Herrmann Joachim R. Kalden V Preface Apoptosis and Autoimmunity. From Mechanisms to Treatments. Edited by J.R. Kalden, M. Herrmann Copyright © 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30442-8 Preface V List of Contributors XVII Part 1 General Features of Apoptosis 1 1 Apoptosis and Autoimmunity 3 Keith Elkon 1.1 Introduction 3 1.2 Autoimmune Diseases Associated with Targeted Cell Destruction 5 1.2.1 What is the Mode of Cell Death? 5 1.2.2 What Cells and What Effector Pathways are Responsible for Cell Death? 6 1.3 Autoimmune Diseases Associated with Enhanced Cell Growth and Survival 7 1.4 Autoimmune Diseases Associated with Abnormal Processing of Dying Cells 7 1.5 Conclusions 9 1.6 References 10 2 Caspase Knockouts: Matters of Life and Death 13 Saquib Lakhani, Binfeng Lu and Richard A. Flavell 2.1 Death, Development and Immune Function 13 2.2 Apoptotic Pathways: from Nematode to Mammals 15 2.3 Triggering a Killer: General Aspects of Caspase Activation 16 2.4 Caspase-1 and -11: More than Mediators of Inflammatory Cytokines? 17 2.5 Caspase-8 and the FAS Signaling Pathway 19 2.6 Caspase-3: The Chief Executioner? 21 2.7 Caspase-9: Mitochondrial Activation and the Apoptosome 22 2.8 Caspase-2: A Duality of Function 24 2.9 Caspase-12: Responding to Stress 25 2.10 Compensatory Caspase Activation: A Caveat to Knockout Analysis 26 2.11 Caspases: More than Simple Killers 27 2.12 Concluding Remarks 28 2.13 References 29 VII Contents Apoptosis and Autoimmunity. From Mechanisms to Treatments. Edited by J.R. Kalden, M. Herrmann Copyright © 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30442-8 Part 2 Clearance of Apoptotic Cells 37 3 Anti-inflammatory and Immunoregulatory Effects of Apoptotic Cells 39 Reinhard E. Voll, Martin Herrmann, Irute Girkontaite, Wasilis Kolowos and Joachim R. Kalden 3.1 Introduction 39 3.2 Anti-inflammatory Effects of Apoptotic Cells on Monocytes/Macrophages 40 3.3 The Role of Anti-inflammatory Cytokines for the Inhibition of Pro-inflammatory Cytokine Production 45 3.4 Monocyte/Macrophage Receptors receiving the Anti-inflammatory Signal from Apoptotic Cells 46 3.5 Intracellular Signaling Events Causing the Anti-inflammatory State in Macrophages 48 3.6 Apoptotic Cells Impair MHC Class II Surface Expression on Monocytes 48 3.7 Influence of Apoptotic Cells on DC Function in Allogeneic MLR 49 3.8 The Presence of Apoptotic Cells can Shift the Th Cell Response towards Th2 50 3.9 Apoptotic Cells Suppress Delayed-type Hypersensitivity (DTH) In Vivo 51 3.10 Necrosis and Inflammation 51 3.11 Implications of the Anti-inflammatory and Immunodulatory Effects of Apoptotic Cells for Health and Disease 53 3.11.1 Apoptosis and Pregnancy 53 3.11.2 Apoptosis and Irradiation 53 3.11.3 Apoptosis and Cancer 53 3.11.4 Apoptosis and Infections 54 3.11.5 Apoptosis and Blood Transfusions 54 3.12 References 55 4 Complement and Apoptosis 57 Dror Mevorach 4.1 Introduction 57 4.2 Programmed Cell Death (PCD) 57 4.3 Complement 59 4.4 Complement and Apoptosis 62 4.4.1 Role of Complement in the Execution Phase 62 4.4.2 Complement Activation by Apoptotic Cells 65 4.5 Apoptosis, Complement and Autoimmunity 68 4.6 References 70 5 Soluble Factors that Bind to Dying Cells Control the Outcome of Corpse Disposal: The Role of Pentraxins, Collectins and Autoantibodies 79 Patrizia Rovere-Querini Contents VIII 5.1 Introduction 79 5.2 Soluble Factors Involved in Apoptotic Cell Recognition and Internalization 76 5.2.1 Corpse Clearance at Rest: Collectins 79 5.2.2 Corpse Clearance at Rest: Cationic Factors and Other PS-binding Moieties 81 5.2.3 Corpse Clearance during Acute Inflammation: Pentraxins 82 5.3 Corpse Clearance in Autoimmune Patients: Autoantibodies 86 5.4 Conclusions 88 5.5 Acknowledgements 89 5.6 References 89 6 The Role of ATP-binding Cassette Transporters in the Clearance of Apoptotic Cells: A Tale of Two Systems 97 Véronique Rigot and Giovanna Chimini 6.1 Introduction 97 6.2 The Family of ABC Transporters 97 6.3 The Case of ABCA1 in Mammals 99 6.3.1 ABCA1 and Reverse Cholesterol Transport 102 6.3.2 ABCA1 and Engulfment 103 6.4 The Case of CED-7 in C. elegans 104 6.5 The Model 106 6.6 References 107 7 Innate Immunity and Apoptosis: CD14-dependent Clearance of Apoptotic Cells 111 Christopher D. Gregory and Andrew Devitt 7.1 Introduction: CD14, A Multifunctional Molecule involved in Innate Immune Responses 111 7.1.1 Background 111 7.1.2 Molecular Structure and Distribution of CD14 111 7.1.3 CD14 as an LPS Receptor that Signals LPS Responses 112 7.1.4 CD14 Binds Multiple and Diverse Ligands 113 7.2 Evidence that Apoptotic Cells Interact with CD14 114 7.2.1 61D3, a CD14 Monoclonal Antibody that Blocks Apoptotic Cell Clearance 114 7.2.2 Exogenous Expression of CD14 in Non-myeloid Cells 114 7.2.3 Apoptotic Cell-associated Ligands of CD14 116 7.3 Mechanisms: Conceptualizing CD14’s Role in Apoptotic Cell Clearance 119 7.3.1 CD14 as a PRR that Recognizes Apoptotic Cell-associated Molecular Patterns (ACAMPs) 119 7.3.2 Differential CD14 Signaling following Ligand Binding 121 7.4 Conclusions: Relative Importance of CD14 in Apoptotic Cell Clearance 122 7.5 References 124 Contents IX Part 3 Autoimmunity Caused by Defective Execution of Apoptosis or Defective Clearance of Apoptotic Cells 133 8 Autoimmune Lymphoproliferative Syndromes (ALPS) 135 Frédérik Rieux-Laucat, Françoise le Deist and Alain Fischer 8.1 Introduction 135 8.2 Death Receptors and Signaling of Apoptosis 135 8.3 Clinical and Immunological Basis of ALPS 138 8.3.1 Definitions 138 8.3.2 Clinical Presentation 138 8.3.2.1 Lymphoproliferation 138 8.3.2.2 Autoimmune Manifestations 139 8.3.2.3 Other Clinical Manifestations 140 8.3.3 Laboratory Findings 140 8.3.3.1 Immunological Data 140 8.3.3.2 Pathological Findings 140 8.3.4 Treatment 141 8.4 Genetic and Molecular Bases of ALPS 141 8.4.1 ALPS 0 142 8.4.2 ALPS Ia 142 8.4.3 ALPS Ib 145 8.4.4 ALPS II 145 8.4.5 ALPS III 146 8.5 Mechanism of Autoimmunity in ALPS 147 8.6 Conclusion 148 8.7 References 149 9 Infection and Inflammation as Cofactors for Autoimmunity of Systemic Lupus Erythematosus Patients 157 Hanns-Martin Lorenz 9.1 Introduction 157 9.2 Infection and Autoimmunity 157 9.3 Infection, Inflammation and SLE: Theory and Practical Aspects 159 9.3.1 Theoretical Considerations for the Pathogenesis of SLE 159 9.3.2 Practical Aspects in Human SLE 163 9.4 Conclusions 164 9.5 References 165 10 Apoptosis in Rheumatoid Arthritis 169 Yuji Yamanishi and Gary S. Firestein 10.1 Introduction 169 10.2 Apoptosis in RA Synovium 171 10.3 Apoptosis in Synovial Fluid T Cells 172 10.4 Regulation of Apoptosis by Cytokines 173 10.5 p53 Mutations in RA Synovium and Fibroblast-like Synoviocytes 174 10.5.1 The Role and Regulation of p53 Tumor Suppressor Protein 174 Contents X

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