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

[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...

[学科分类] 生理学

[关键词] maturation;blood;bone marrow;tissue;HIF‐1αHIF‐2α