Flieger Oliver, Engling André, Bucala Richard, Lue Hongqi, Nickel Walter, Bernhagen Jürgen
Institute for Interfacial Engineering, University of Stuttgart, Nobelstrasse 12, 70569 Stuttgart, Germany.
FEBS Lett. 2003 Sep 11;551(1-3):78-86. doi: 10.1016/s0014-5793(03)00900-1.
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.
细胞因子巨噬细胞移动抑制因子（MIF）由免疫细胞和某些其他细胞类型诱导分泌，以关键方式参与宿主免疫反应的调节。然而，MIF不含N端信号序列，其分泌机制尚不清楚。在此，我们在内毒素刺激的THP-1单核细胞模型中表明，MIF不进入内质网，且莫能菌素或布雷菲德菌素A不抑制MIF分泌，这表明MIF分泌通过非经典输出途径发生。格列本脲和丙磺舒而非其他典型的非经典蛋白质输出抑制剂强烈阻断MIF分泌，表明MIF的输出途径涉及ABCA1转运蛋白。
