ORIGINANDCONSEQUENCESOFNECROINFLAMMATIONMaysaSarhan,WalterG.Land,WulfTonnus,ChristianP.Hugo,andXAndreasLinkermannDivisionofNephrologyandDialysis,DepartmentofMedicineIII,MedicalUniversityVienna,Vienna,Austria;INSERMUMR_S1109,LaboratoryofExcellenceTransplantex,UniversityofStrasbourg,Strasbourg,France;GermanAcademyofTransplantationMedicine,Munich,Germany;andDivisionofNephrology,DepartmentofInternalMedicineIII,UniversityHospitalCarlGustavCarusattheTechnischeUniversitätDresden,Dresden,GermanyLSarhanM,LandWG,TonnusW,HugoCP,LinkermannA.OriginandConsequencesofNecroinflammation.PhysiolRev98:727–780,2018.PublishedFebruary21,2018;doi:10.1152/physrev.00041.2016.—Whencellsundergonecroticcelldeathineitherphysiologicalorpathophysiologicalsettingsinvivo,theyreleasehighlyimmuno-genicintracellularmoleculesandorganellesintotheinterstitiumandtherebyrepresentthestrongestknowntriggeroftheimmunesystem.Withourincreasingunderstandingofnecrosisasaregulatedandgeneticallydeterminedprocess(RN,regulatednecrosis),necrosisandnecroinflamma-tioncanbepharmacologicallyprevented.Thisreviewdiscussesourcurrentknowledgeaboutsignalingpathwaysofnecroticcelldeathastheoriginofnecroinflammation.MultiplepathwaysofRNsuchasnecroptosis,ferroptosis,andpyroptosishavebeenevolutionaryconservedmostlikelybecauseoftheirdifferencesinimmunogenicity.Astheconsequenceofnecrosis,however,allnecroticcellsreleasedamageassociatedmolecularpatterns(DAMPs)thathavebeenextensivelyinvestigatedoverthelasttwodecades.Analysisofnecroinflammationallowscharacterizingspecificsignaturesforeachpartic-ularpathwayofcelldeath.WhileallRN-pathwayssharethereleaseofDAMPsingeneral,mostofthemactivelyregulatetheimmunesystembytheadditionalexpressionand/ormaturationofeitherpro-oranti-inflammatorycytokines/chemokines.Inaddition,DAMPshavebeendemonstratedtomodulatetheprocessofregeneration.Forthepurposeofbetterunderstandingofnecroinflammation,weintroduceanovelclassificationofDAMPsinthisreviewtohelpdetecttherelativecontributionofeachRN-pathwaytocertainphys...
