Hypoxia: how does the monocyte‐macrophage system respond to changes in oxygen availability?

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

关键词: maturation;    blood;    bone marrow;    tissue;    HIF‐;    1α;    HIF‐;    2α;   

DOI  :  10.1189/jlb.1212627

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Hypoxiaisanimportantfeatureofinflamedtissue,suchastheRAjoint.Activatedmonocytes/macrophagesandendothelialcellsplayapivotalroleinthepathogenesisofRA,implicatedinthemechanismofinflammationanderosion.Duringdevelopment,myeloidprogenitorcellssequentiallygiverisetomonoblasts,promonocytes,andmonocytesthatarereleasedfromthebonemarrowintothebloodstream.Afterextravasation,monocytesdifferentiateintolong‐lived,tissue‐specificmacrophagesorDCs.Theeffectofdifferentoxygenconcentrationsexperiencedbythesecellsduringmaturationrepresentsanovelaspectofthisdevelopmentalprocess.Ininflamedjointtissue,themicrovasculararchitectureishighlydysregulated;thus,efficiencyofoxygensupplytothesynoviumispoor.Therefore,invadingcellsmustadaptinstantaneouslytochangesintheoxygenlevelofthemicroenvironment.Angiogenesisisanearlyeventintheinflammatoryjoint,whichisimportantinenablingactivatedmonocytestoenterviaendothelialcellsbyactiverecruitmenttoexpandthesynoviumintoa“pannus”,resultingincartilagedegradationandbonedestruction.Theincreasedmetabolicturnoveroftheexpandingsynovialpannusoutpacesthedysfunctionalvascularsupply,resultinginhypoxia.Theabnormalbioenergeticsofthemicroenvironmentfurtherpromotessynovialcellinvasiveness.InRA,jointhypoxiarepresentsapotentialthreattocellfunctionandsurvival.Notably,oxygenavailabilityisacrucialparameterinthecellularenergymetabolism,itselfanimportantfactorindeterminingthefunctionofimmunecells...

【 授权许可】

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