M‐sec regulates polarized secretion of inflammatory endothelial chemokines and facilitates CCL2‐mediated lymphocyte transendothelial migration

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

关键词: endothelial cells;    inflammation;    cytokines;    leukocyte trafficking;   

DOI  :  10.1189/jlb.3VMA0915-427R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ActivationofendothelialcellsbyIL‐1βtriggerstheexpressionofmultipleinflammatorycytokinesandleukocyte‐attractingchemokines.Themachineriesinvolvedinthesecretionoftheseinducibleproteinsarepoorlyunderstood.Withtheuseofgenome‐widetranscriptionalanalysisofinflamedhumandermalmicrovascularendothelialcells,weidentifiedseveralIL‐1β−inducedcandidateregulatorsofthesemachineriesandchosetofocusourstudyonTNF‐α‐inducedprotein2(myeloid‐secretory).Thesilencingofmyeloid‐secretorydidnotaffecttheabilityofinflamedendothelialcellstosupporttheadhesionandcrawlingofeffectorTlymphocytes.However,theabilityoftheselymphocytestocompletetransendothelialmigrationacrossmyeloid‐secretory‐silencedhumandermalmicrovascularendothelialcellswasinhibitedsignificantly.TheseobservedeffectsonlymphocytetransendothelialmigrationwererecoveredcompletelywhenexogenouspromigratorychemokineCXCL12wasoverlaidontheendothelialbarrier.Apolarizedsecretionassaysuggestedthatthesilencingofendothelialmyeloid‐secretoryimpairsTeffectortransendothelialmigrationbyreducingthepreferentialsecretionofendothelial‐producedCCL2,akeytransendothelialmigration‐promotingchemokinefortheselymphocytes,intothebasolateralendothelialcompartment.Myeloid‐secretorysilencingalsoimpairedthepreferentialsecretionofotherendothelial‐producedinflammatorychemokines,aswellascytokines,suchasIL‐6andGM‐CSF,intothebasolateralendothelialcompartment.Thisisthefirstevidenceofanovelinflammation‐induciblemachinerythatregulatespolarizedsecretionofendothelialCCL2andotherinflammatorychemokinesandcytokinesintobasolateralendothelialcompartmentsandfacilitatestheabilityofendothelialCCL2topromoteTcelltransendothelialmigration...

【 授权许可】

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