Platelets are a previously unrecognised source of MIF
Platelets are a previously unrecognised source of MIF
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DOI：
10.1160/th13-01-0049
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发表时间：
2013-11-01
影响因子：
6.7
通讯作者：
Bernhagen, Juergen
中科院分区：
文献类型：
--
作者：
Struessmann, Tim;Tillmann, Sabine;Bernhagen, Juergen
巨噬细胞移动抑制因子（MIF）是一种具有趋化因子样功能的炎性细胞因子，在动脉粥样硬化形成中起作用。MIF由多种细胞分泌，包括内皮细胞和巨噬细胞。血小板是另一种在动脉粥样硬化形成中起作用的突出细胞类型，并且是致动脉粥样硬化趋化因子的丰富来源。我们询问血小板是否表达和分泌MIF。作为比较，测定CXCL 12释放。我们研究了血小板/巨核细胞中MIF的亚细胞定位，研究了其与其他血小板衍生介质的共定位，并询问血小板是否含有MIF mRNA。此外，我们探讨了血小板衍生的MIF在炎症细胞募集中的功能作用。采用Western blot和ELISA方法检测人和小鼠血小板中MIF蛋白的表达。应用共聚焦显微镜，发现MIF定位于颗粒状结构，但不与已知的血小板细胞因子共定位。qPCR显示血小板含有低水平的MIF mRNA。从人血小板上清液的ELISA测量结果表明，而凝血酶和胶原蛋白触发释放的MIF和CXCL 12，ADP和氧化LDL促进CXCL 12，但不是MIF分泌。使用Transwell试验，我们证明，血小板上清液促进单核细胞趋化性，这是通过中和MIF抗体阻断。这是第一份证明活化血小板分泌MIF的报告，表明血小板是炎症过程中以前未认识到的MIF来源。MIF和CXCL 12的分泌有不同的激活刺激。刺激血小板上清液的趋化能力的相当大一部分是由MIF贡献的，这表明血小板衍生的MIF在致动脉粥样硬化细胞募集中的作用。
Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine with chemokine-like functions and a role in atherogenesis. MIF is secreted by various cells including endothelial cells and macrophages. Platelets are another prominent cell type with a role in atherogenesis and are a rich source of atherogenic chemokines. We asked whether platelets express and secrete MIF. In comparison, CXCL12 release was determined. We examined the subcellular localisation of MIF in platelets/megakaryocytes, studied its co-localisation with other platelet-derived mediators and asked whether platelets contain MIF mRNA. Moreover, we probed the functional role of platelet-derived MIF in inflammatory cell recruitment. Using Western blot and ELISA, we demonstrated and quantitated MIF protein in human and mouse platelets. Applying confocal-microscopy, MIF was found to localise in granular-like structures, but did not co-localise with known platelet cytokines. qPCR indicated that platelets contain low levels of MIF mRNA. ELISA measurements from human platelet supernatants showed that, whereas thrombin and collagen triggered the release of MIF and CXCL12, ADP and oxidised LDL promoted CXCL12 but not MIF secretion. Using Transwell assays, we demonstrated that platelet supernatants promoted monocyte chemotaxis and that this was blocked by neutralising MIF antibodies. This is the first report demonstrating MIF secretion from activated platelets, suggesting that platelets are a previously unrecognised source of MIF in inflammatory processes. There are distinct activating stimuli for MIF and CXCL12 secretion. A substantial portion of the chemotactic capacity of stimulated platelet supernatants is contributed by MIF, suggesting a role for platelet-derived MIF in atherogenic cell recruitment.