The development of giant phagocytes in long‐term neutrophil cultures

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: apoptosis;    autophagy;    oxidized LDL;    reactive oxygen species;    LC3B;    LC3B inhibitors;   

DOI  :  10.1189/jlb.0813437

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Wetestedthehypothesisthatinlong‐termcultureconditions,someneutrophilsremainviableandparticipateindebrisclearance,andautophagyisinvolvedintheirprolongedsurvival.Neutrophils,classifiedasprofessionalphagocytes,havetheshortesthalf‐lifeamongleukocytesandareconstitutivelycommittedtoapoptosis.ApoptoticneutrophilsareactivelyremovedbyMφ/DCs.However,earlyandacuteinflammatoryinfiltratesprimarilyconsistofneutrophils.Recently,neutrophilsweresuggestedtofacilitatedebrisclearanceatinflammatorysiteswhentheMφ/DCsystemisinsufficient.Here,purifiedCD15+/CD66b+/CD63+neutrophilswerefollowedupto7daysincultureusinglight,time‐lapse,andconfocalmicroscopy.After3daysinculture,Annexin‐V−/LC3B+largevacuolatedcells,engulfingcellularresidues,werenotedamongapoptoticneutrophilsandcelldebris.Thereafter,thesecellswerevastlyenlargedandexhibitedaneutrophilicphenotype(CD15+/CD63+/MPO+/CD66b+),phagocytosis,andoxidativeburstactivity.TheyalsoexpressedCD68scavengerreceptorsandinternalizedoxLDL.But,unlikeinfreshneutrophilsorculturedmonocytes,oxLDLtreatmentincreasedtheirROSproduction.Additionally,thesephagocytescontainedLC3B‐coatedvacuolesandLC3Baggregates,indicatingtheactivationofautophagy.AnintensiveLC3BaccumulationwasalsonotedduringoxLDLinternalization.Importantly,theinhibitionofautophagyby3‐MAorBafA1preventedtheirdevelopment.Inconclusion,theinternalizationofneutrophilremnantsmayinduceactivationofautophagicmechanismsinsomeneutrophilsubsetsorprecursors.Thismayleadtocelladaptationandsurvival,resultingintheirtransformationintolong‐livedGφandpotentiallysuggestingtheirinvolvementininflammatory/anti‐inflammatoryprocesses...

【 授权许可】

CC BY