Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
M‐sec regulates polarized secretion of inflammatory endothelial chemokines and facilitates CCL2‐mediated lymphocyte transendothelial migration | |
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】
CC BY
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO201901235715244ZK.pdf | 2505KB | download |