PH81CH17_LeeARI16November201813:53AnnualReviewofPhysiologyCellDeathintheLung:TheApoptosis–NecroptosisAxisMaorSauler,IsabelS.Bazan,andPattyJ.LeeDepartmentofMedicine,YaleSchoolofMedicine,NewHaven,Connecticut06520,USA;email:patty.lee@yale.eduAnnu.Rev.Physiol.2019.81:17.1–17.28TheAnnualReviewofPhysiologyisonlineatphysiol.annualreviews.orghttps://doi.org/10.1146/annurev-physiol-020518-114320Copyrightc⃝2019byAnnualReviews.AllrightsreservedKeywordsapoptosis,necroptosis,idiopathicpulmonaryfibrosis,chronicobstructivepulmonarydisease,asthma,pulmonaryarterialhypertension,acuterespiratorydistresssyndromeAbstractRegulatedcelldeathisamajormechanismtoeliminatedamaged,infected,orsuperfluouscells.Previously,apoptosiswasthoughttobetheonlyregulatedcelldeathmechanism;however,newmodalitiesofcaspase-independentreg-ulatedcelldeathhavebeenidentified,includingnecroptosis,pyroptosis,andautophagiccelldeath.Asanunderstandingofthecellularmechanismsthatmediateregulatedcelldeathcontinuestogrow,thereisincreasingevidencethatthesepathwaysareimplicatedinthepathogenesisofmanypulmonarydisorders.Thisreviewsummarizesourunderstandingofregulatedcelldeathasitpertainstothepathogenesisofchronicobstructivepulmonarydisease,asthma,idiopathicpulmonaryfibrosis,acuterespiratorydistresssyndrome,andpulmonaryarterialhypertension.17.1ReviewinAdvancefirstpostedonNovember28,2018.(Changesmaystilloccurbeforefinalpublication.)Annu.Rev.Physiol.2019.81.Downloadedfromwww.annualreviews.orgAccessprovidedbyUniversityofWinnipegon11/30/18.Forpersonaluseonly.PH81CH17_LeeARI16November201813:53INTRODUCTIONThehealthandsurvivalofmulticellularorganismsrelyontheabilitytoeliminatedamaged,infected,orsuperfluouscells.Therefore,multicellularorganismspossessgeneticallyencodedmechanismsviawhichcellscanundergoregulatedcelldeath(RCD).RCDoccursaspartofnormalphysiologicprogramming,includingorgandevelopmentandepithelialrenewal.Italsooccursincellsthatcannotmitigatestressorsthatthreatentissuehomeostasis,e.g.,cellsinfectedbyintracellularpathogens...
