Apoptosis and Autoimmunity: From Mechanisms to Treatments PDF
Preview Apoptosis and Autoimmunity: From Mechanisms to Treatments
Apoptosis and Autoimmunity Editedby M.HerrmannandJ.R. Kalden ApoptosisandAutoimmunity.FromMechanismstoTreatments. EditedbyJ.R.Kalden,M.Herrmann Copyright©2003WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim ISBN:3-527-30442-8 Further titles of interest Stuhler,G./Walden,P.(Eds.) Cancer Immune Therapy CurrentandFutureStrategies 2000, ISBN3-527-30441-X Stewart,C.C./Nicholson,J.K.A.(Eds.) Immunophenotyping Cytometric CellularAnalysis 2000,ISBN0-471-23957-7 Freshney,R.I. Culture of Animal Cells AManualof Basic Technique 2000, ISBN0-471-34889-9 Krauss,G./Cooper,B.L./Schönbrunner,N. Biochemistry of Signal Transduction and Regulation Building Blocks andFineChemicals 2001, ISBN3-527-30378-2 Apoptosis and Autoimmunity Edited by M. Herrmann and J.R. Kalden Prof.Dr.Dr.JoachimR.Kalden (cid:1) This book was carefully produced. Nevertheless, UniversityofErlangen-Nuremberg authors,editorsandpublisherdonotwarrantthe DepartmentofInternalMedicineIII informationcontainedthereintobefreeofer- andInstituteforClinicalImmunology rors.Readersareadvisedtokeepinmindthat Krankenhausstraße12 statements,data,illustrations,proceduraldetails 91054Erlangen,Germany orotheritemsmayinadvertentlybeinaccurate. Dr.Dr.MartinHerrmann UniversityofErlangen-Nuremberg InstituteforClinicalImmunology LibraryofCongressCardNo.:appliedfor Krankenhausstraße12 91054Erlangen,Germany BritishLibraryCataloguing-in-Publication Data:Acataloguerecordforthisbookisavailable fromtheBritishLibrary. Bibliographicinformationpublishedby DieDeutscheBibliothek DieDeutscheBibliothekliststhispublicationin theDeutscheNationalbibliografie;detailedbiblio- graphicdataisavailableintheInternetat <http://dnb.ddb.de>. ©2003WILEY-VCHVerlagGmbH&Co.KGaG, Weinheim Allrightsreserved(includingthoseoftranslation inotherlanguages).Nopartofthisbookmaybe reproducedinanyform–nortransmittedor translatedintoamachinelanguagewithoutwrit- tenpermissionfromthepublishers.Registered names,trademarks,etc.usedinthisbook,even whennotspecificallymarkedassuch,arenotto beconsideredunprotectedbylaw. PrintedintheFederalRepublicofGermany Printedonacid-freepaper Composition K+VFotosatzGmbH,Beerfelden Printing betz-druckgmbh,Darmstadt Bookbinding GroßbuchbindereiJ.Schäffer GmbH&Co.KG,Grünstadt ISBN 3-527-30442-8 V Preface More than 100 years ago Paul Ehrlich coined the expression ‘horror autotoxicus’ implicating the existenceof autoimmune diseases.After the firstdescriptionof 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- cessisnotonly avital mechanismsustaining homeostasisinthe regulation ofim- 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 discussionon apoptosisand its rolein 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 ofthis book. Erlangen, July 2002 Martin Herrmann Joachim R. Kalden ApoptosisandAutoimmunity.FromMechanismstoTreatments. EditedbyJ.R.Kalden,M.Herrmann Copyright©2003WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim ISBN:3-527-30442-8 VII Contents Preface V ListofContributors XVII Part1 GeneralFeaturesofApoptosis 1 1 Apoptosis andAutoimmunity 3 Keith Elkon 1.1 Introduction 3 1.2 Autoimmune DiseasesAssociatedwith Targeted Cell Destruction 5 1.2.1 What isthe Modeof Cell Death? 5 1.2.2 What Cellsand What EffectorPathways are Responsible forCell Death? 6 1.3 Autoimmune DiseasesAssociatedwith Enhanced Cell Growth and Survival 7 1.4 Autoimmune DiseasesAssociatedwith Abnormal Processing ofDying Cells 7 1.5 Conclusions 9 1.6 References 10 2 CaspaseKnockouts: MattersofLifeandDeath 13 Saquib Lakhani, Binfeng Lu and Richard A. Flavell 2.1 Death, Developmentand Immune Function 13 2.2 Apoptotic Pathways: fromNematode to Mammals 15 2.3 Triggering a Killer: General Aspects of CaspaseActivation 16 2.4 Caspase-1and -11: Morethan MediatorsofInflammatory Cytokines? 17 2.5 Caspase-8and the FAS Signaling Pathway 19 2.6 Caspase-3:The Chief Executioner? 21 2.7 Caspase-9:MitochondrialActivation and the Apoptosome 22 2.8 Caspase-2:A Duality of Function 24 2.9 Caspase-12:Responding to Stress 25 2.10 Compensatory CaspaseActivation:A Caveat to Knockout Analysis 26 2.11 Caspases:Morethan Simple Killers 27 2.12 ConcludingRemarks 28 2.13 References 29 ApoptosisandAutoimmunity.FromMechanismstoTreatments. EditedbyJ.R.Kalden,M.Herrmann Copyright©2003WILEY-VCHVerlagGmbH&Co.KGaA,Weinheim ISBN:3-527-30442-8 VIII Contents Part2 ClearanceofApoptotic Cells 37 3 Anti-inflammatory andImmunoregulatoryEffects ofApoptotic Cells 39 Reinhard E. Voll,Martin Herrmann,IruteGirkontaite, WasilisKolowos and Joachim R. Kalden 3.1 Introduction 39 3.2 Anti-inflammatory EffectsofApoptotic Cells on Monocytes/Macrophages 40 3.3 The Role of Anti-inflammatory Cytokines for the Inhibition ofPro-inflammatory Cytokine Production 45 3.4 Monocyte/Macrophage Receptorsreceivingthe Anti-inflammatory Signal fromApoptotic Cells 46 3.5 Intracellular Signaling EventsCausing the Anti-inflammatory State inMacrophages 48 3.6 ApoptoticCellsImpairMHCClassII SurfaceExpression onMonocytes 48 3.7 Influence ofApoptoticCellsonDCFunctioninAllogeneicMLR 49 3.8 The PresenceofApoptoticCellscanShift the T CellResponse h towardsT 2 50 h 3.9 ApoptoticCellsSuppressDelayed-typeHypersensitivity(DTH) InVivo 51 3.10 NecrosisandInflammation 51 3.11 Implications ofthe Anti-inflammatory andImmunodulatory EffectsofApoptoticCellsforHealth andDisease 53 3.11.1 ApoptosisandPregnancy 53 3.11.2 ApoptosisandIrradiation 53 3.11.3 ApoptosisandCancer 53 3.11.4 ApoptosisandInfections 54 3.11.5 ApoptosisandBloodTransfusions 54 3.12 References 55 4 ComplementandApoptosis 57 Dror Mevorach 4.1 Introduction 57 4.2 ProgrammedCellDeath (PCD) 57 4.3 Complement 59 4.4 Complement andApoptosis 62 4.4.1 RoleofComplement inthe ExecutionPhase 62 4.4.2 Complement ActivationbyApoptoticCells 65 4.5 Apoptosis,Complement andAutoimmunity 68 4.6 References 70 5 SolubleFactorsthatBindtoDyingCellsControltheOutcome ofCorpseDisposal: TheRoleofPentraxins,CollectinsandAutoantibodies 79 Patrizia Rovere-Querini Contents IX 5.1 Introduction 79 5.2 Soluble FactorsInvolvedin Apoptotic Cell Recognition and Internalization 76 5.2.1 CorpseClearance at Rest: Collectins 79 5.2.2 CorpseClearanceat Rest:CationicFactorsandOtherPS-binding Moieties 81 5.2.3 CorpseClearanceduring AcuteInflammation: Pentraxins 82 5.3 CorpseClearanceinAutoimmunePatients:Autoantibodies 86 5.4 Conclusions 88 5.5 Acknowledgements 89 5.6 References 89 6 TheRoleofATP-bindingCassetteTransportersintheClearance ofApoptotic Cells:ATaleofTwoSystems 97 VéroniqueRigot and Giovanna Chimini 6.1 Introduction 97 6.2 The Family ofABC Transporters 97 6.3 The CaseofABCA1 in Mammals 99 6.3.1 ABCA1 andReverseCholesterolTransport 102 6.3.2 ABCA1 and Engulfment 103 6.4 The CaseofCED-7in C. elegans 104 6.5 The Model 106 6.6 References 107 7 InnateImmunityandApoptosis: CD14-dependentClearanceofApoptotic Cells 111 ChristopherD. Gregoryand AndrewDevitt 7.1 Introduction: CD14, A Multifunctional Moleculeinvolved in Innate Immune Responses 111 7.1.1 Background 111 7.1.2 MolecularStructureandDistributionofCD14 111 7.1.3 CD14asanLPS Receptorthat Signals LPS Responses 112 7.1.4 CD14BindsMultiple andDiverseLigands 113 7.2 Evidencethat Apoptotic Cells Interact with CD14 114 7.2.1 61D3, a CD14 MonoclonalAntibody that BlocksApoptotic Cell Clearance 114 7.2.2 ExogenousExpressionofCD14 in Non-myeloidCells 114 7.2.3 ApoptoticCell-associatedLigandsofCD14 116 7.3 Mechanisms:Conceptualizing CD14’sRoleinApoptotic CellClearance 119 7.3.1 CD14asaPRR that RecognizesApoptoticCell-associated MolecularPatterns(ACAMPs) 119 7.3.2 DifferentialCD14Signaling following Ligand Binding 121 7.4 Conclusions:RelativeImportanceofCD14inApoptotic CellClearance 122 7.5 References 124 X Contents Part3 AutoimmunityCausedbyDefective Execution ofApoptosis orDefective ClearanceofApoptotic Cells 133 8 AutoimmuneLymphoproliferative Syndromes(ALPS) 135 FrédérikRieux-Laucat,Françoise leDeistand AlainFischer 8.1 Introduction 135 8.2 DeathReceptorsandSignaling ofApoptosis 135 8.3 ClinicalandImmunological BasisofALPS 138 8.3.1 Definitions 138 8.3.2 ClinicalPresentation 138 8.3.2.1 Lymphoproliferation 138 8.3.2.2 Autoimmune Manifestations 139 8.3.2.3 OtherClinical Manifestations 140 8.3.3 LaboratoryFindings 140 8.3.3.1 Immunological Data 140 8.3.3.2 Pathological Findings 140 8.3.4 Treatment 141 8.4 GeneticandMolecularBasesofALPS 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 MechanismofAutoimmunity inALPS 147 8.6 Conclusion 148 8.7 References 149 9 InfectionandInflammation asCofactors forAutoimmunity ofSystemicLupusErythematosus Patients 157 Hanns-Martin Lorenz 9.1 Introduction 157 9.2 InfectionandAutoimmunity 157 9.3 Infection,Inflammation andSLE:TheoryandPracticalAspects 159 9.3.1 TheoreticalConsiderationsforthe PathogenesisofSLE 159 9.3.2 PracticalAspectsinHuman SLE 163 9.4 Conclusions 164 9.5 References 165 10 Apoptosis inRheumatoid Arthritis 169 Yuji Yamanishi and Gary S. Firestein 10.1 Introduction 169 10.2 ApoptosisinRA Synovium 171 10.3 ApoptosisinSynovialFluid T Cells 172 10.4 Regulation ofApoptosisbyCytokines 173 10.5 p53Mutations inRA SynoviumandFibroblast-likeSynoviocytes 174 10.5.1 The RoleandRegulation ofp53TumorSuppressorProtein 174 Contents XI 10.5.2 p53ProteinExpressioninInflammation 175 10.5.3 p53Mutations inRA SynovialTissue 176 10.5.4 PossibleMechanismofOccurrenceofp53Mutations 176 10.5.5 Functionofp53Mutations inRA Synovial Cells 177 10.6 Fas-FasLigand (FasL)ApoptoticPathway inRA 177 10.6.1 FasandFasL 177 10.6.2 Fas-FasLExpressioninSynovium 178 10.6.3 Fas-FasLExpressioninSynovial FluidCells 178 10.6.4 sFas 178 10.6.5 sFasL 179 10.6.6 Fas-MediatedApoptosis 179 10.7 Therapeutic TargetofMoleculesforInducing Apoptosis inSynovialTissues 180 10.7.1 Fas-FasLandRelatedMolecules 180 10.7.2 NuclearFactor(NF)-(cid:1)BandRelatedMolecules 181 10.7.3 p53TumorSuppressorGene 182 10.7.4 Proteasome 182 10.8 Conclusion 182 10.9 References 183 11 SystemicLupusErythematosus 187 Thomas D. Beyer, SusanneKuenkele,Udo S. Gaipl,WasilisKolowos, Reinhard E. Voll,Irith Baumann, Joachim R. Kalden and Martin Herrmann 11.1 Introduction 187 11.2 InvolvementofBCellsinthe DevelopmentofSLE 187 11.3 InvolvementofT Cellsinthe DevelopmentofSLE 188 11.4 GeneticFactorsforthe DevelopmentofSLE 189 11.5 Animal Modelsforthe Immunogenicity ofDying Cells 189 11.6 PhagocytosisofApoptoticCells 190 11.7 ReducedPhagocytosisofApoptoticCellsinSLE Patients Challenges T CellTolerance 190 11.7.1 IncreasedApoptosisinSLEPatients? 190 11.7.2 ReducedPhagocytosisofApoptoticCellsbyInVitro GeneratedMacrophagesfromSLEPatients 191 11.7.3 Hypothesis:AccumulationofSecondaryNecroticCellsChallenges T CellToleranceinSLE 191 11.8 The GerminalCenterReaction 193 11.9 ReducedPhagocytosisofApoptoticCellsinSLE PatientsChallenges B CellTolerance 196 11.9.1 The NumberofTingibleBodyMacrophagesisReduced inthe GerminalCentersofSLEPatients 196 11.9.2 AccumulationofApoptoticCell-DerivedNuclearFragments inthe GerminalCentersofSLEPatients 197
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