Regulated secretion of macrophage migration inhibitory factor is mediated by a non‐classical pathway involving an ABC transporter

FEBS Letters

Engling, André⁴  Nickel, Walter⁴  Flieger, Oliver³  Lue, Hongqi¹  Bucala, Richard²  Bernhagen, Jürgen³ 

[1] Unit of Biochemistry and Molecular Cell Biology, Institute of Biochemistry, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany;Department of Medicine and Pathology, Yale University School of Medicine, New Haven, CT 06520-8031, USA;Institute for Interfacial Engineering, University of Stuttgart and Fraunhofer Institute of Biotechnology, Nobelstrasse 12, 70569 Stuttgart, Germany;Biochemie-Zentrum Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany

关键词: MIF;    Cytokine;    Nonclassical secretion;    Leaderless secretory protein;    ABC transporter;    ABC transporter;    ATP binding cassette transporter;    BFA;    brefeldin A;    BSP;    bromosulfalein;    CHX;    cycloheximide;    CCCH;    carbonyl cyanide m-chlorophenyl hydrazone;    DIDS;    4;    4′-diisothiocyanato-stilbene-2.2′-disulfonic acid;    ER;    endoplasmatic reticulum;    IVT;    in vitro transcription/translation;    FCS;    fetal calf serum;    LDH;    lactate dehydrogenase;    LLS;    leaderless secretory protein;    LPS;    lipopolysaccharide;    MA;    methylamine;    MIF;    macrophage migration inhibitory factor;    Phen;    1;    10-phenanthroline;    Trx;    thioredoxin;    Vera;    verapamil;   

DOI  :  10.1016/S0014-5793(03)00900-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The cytokine macrophage migration inhibitory factor (MIF) is inducibly secreted by immune cells and certain other cell types to critically participate in the regulation of the host immune response. However, MIF does not contain a N-terminal signal sequence and the mechanism of MIF secretion is unknown. Here we show in a model of endotoxin-stimulated THP-1 monocytes that MIF does not enter the endoplasmatic reticulum and that MIF secretion is not inhibited by monensin or brefeldin A, demonstrating that MIF secretion occurs via a non-classical export route. Glyburide and probenicide but not other typical inhibitors of non-classical protein export strongly block MIF secretion, indicating that the export pathway of MIF involves an ABCA1 transporter.

【 授权许可】

Unknown