Regulated secretion of macrophage migration inhibitory factor is mediated by a non-classical pathway involving an ABC transporter.
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.
Flieger
Oliver
O
Institute for Interfacial Engineering, University of Stuttgart, Nobelstrasse 12, 70569 Stuttgart, Germany.
Engling
André
A
Bucala
Richard
R
Lue
Hongqi
H
Nickel
Walter
W
Bernhagen
Jürgen
J
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000502:physiology*; D000595:Amino Acid Sequence; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000737:chemistry / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D011339:Probenecid / Q000494:pharmacology; D021381:Protein Transport
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D011339:Probenecid; D005905:Glyburide