Low‐density lipoprotein receptor‐related protein 1 mediates α1‐antitrypsin internalization in CD4+ T lymphocytes

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

关键词: clathrin‐;    dependent endocytosis;    endosome;    lysosome;    HIV‐;    1;    NF‐;    κ;    B;    Iκ;    Bα;   

DOI  :  10.1189/jlb.2A0515-209R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Inα1‐antitrypsin–deficientHIVpatients,anaccelerateddeclineofCD4+Tcellnumbersisobserved,suggestingthatα1‐antitrypsinisapotentialendogenousHIVinhibitor.IninfectedTlymphocytes,α1‐antitrypsinpotentlyblocksNF‐κBactivationandHIV‐1replicationbydirectlyinteractingwithIκBαinthecytosol,therebyalteringitsubiquitinationpattern.However,themechanismofα1‐antitrypsinentryintothecytosol,whereIκBαlocates,remainsunclear.Inthepresentstudy,weinvestigatedthemechanismofα1‐antitrypsininternalizationinCD4+Tcells.Thus,primaryCD4+TcellswereinfectedwithHIV‐1andthenincubatedwithα1‐antitrypsintodetectitsinternalization.WefoundthatCD4+Tcellsinternalizedα1‐antitrypsinthroughaclathrin‐dependentendocytosisprocess.Next,intracellularα1‐antitrypsinexertedtheinhibitoryeffectonNF‐κBactivationandHIV‐1replication.OnprimaryCD4+Tcells,α1‐antitrypsininteractedwithlow‐densitylipoproteinreceptor‐relatedprotein1toinitiatetheinternalization.InsideCD4+Tlymphocytes,α1‐antitrypsinwastransportedfromtheendosometothelysosomeandthenreleasedintothecytosol,whereitispossibleforα1‐antitrypsintodirectlyinteractwithIκBα.Theseresultstogethersuggestthatα1‐antitrypsininternalizationisaclathrin‐dependentandlow‐densitylipoproteinreceptor‐relatedprotein1–mediatedendocytosisprocess.Internalizedα1‐antitrypsinistransportedthroughtheendosome–lysosome–cytosolroutinetointeractwithcytosolicIκBαandblockNF‐κBactivationandHIV‐1replication...

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