Macrophage migration inhibitory factor induces macrophage recruitment via CC chemokine ligand 2
Macrophage migration inhibitory factor induces macrophage recruitment via CC chemokine ligand 2
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DOI：
10.4049/jimmunol.177.11.8072
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发表时间：
2006-12-01
影响因子：
4.4
通讯作者：
Hickey, Michael J.
中科院分区：
文献类型：
--
作者：
Gregory, Julia L.;Morand, Eric F.;Hickey, Michael J.
巨噬细胞移动抑制因子（MIF）最初是由于其在体外抑制巨噬细胞随机移动的能力而被鉴定的。MIF现在被认为是一系列炎症性疾病的重要介质。我们最近观察到，MIF的缺乏与一系列炎症介质诱导的白细胞-内皮细胞相互作用的减少有关，这表明MIF在炎症反应期间起作用的一种机制是促进白细胞募集。然而，目前尚不清楚MIF是否能够独立于额外的炎症刺激诱导白细胞募集。在这项研究中，我们报告，MIF是能够诱导白细胞粘附和移行在毛细血管后微静脉在体内。此外，对MIF应答的白细胞主要是单核细胞/巨噬细胞谱系的CD 68（+）细胞。抗单核细胞选择性趋化因子CCL 2（JE[MCP-1]）及其受体CCR 2的抗体，而不是CCL 3和CXCL 2，显著抑制MIF诱导的单核细胞粘附和迁移。CCL 2（-/-）小鼠在MIF诱导的募集中显示出类似的减少，表明CCL 2在MIF诱导的应答中起关键作用。这一假设得到了MIF诱导原代微血管内皮细胞释放CCL 2的研究结果的支持。这些数据证明了这种多效性细胞因子以前未被认识到的功能：诱导单核细胞迁移到组织中。这种功能可能对MIF促进动脉粥样硬化和类风湿性关节炎等疾病的能力至关重要，其中巨噬细胞是关键参与者。
Macrophage migration inhibitory factor (MIF) was originally identified for its ability to inhibit the random migration of macrophages in vitro. MIF is now recognized as an important mediator in a range of inflammatory disorders. We recently observed that the absence of MIF is associated with a reduction in leukocyte-endothelial cell interactions induced by a range of inflammatory mediators, suggesting that one mechanism whereby MIF acts during inflammatory responses is by promoting leukocyte recruitment. However, it is unknown whether MIF is capable of inducing leukocyte recruitment independently of additional inflammatory stimuli. In this study, we report that MIF is capable of inducing leukocyte adhesion and transmigration in postcapillary venules in vivo. Moreover, leukocytes recruited in response to MIF were predominantly CD68(+) cells of the monocyte/macrophage lineage. Abs against the monocyte-selective chemokine CCL2 (JE[MCP-1) and its receptor CCR2, but not CCL3 and CXCL2, significantly inhibited MIF-induced monocyte adhesion and transmigration. CCL2(-/-) mice displayed a similar reduction in MIF-induced recruitment indicating a critical role of CCL2 in the MIF-induced response. This hypothesis was supported by findings that MIF induced CCL2 release from primary microvascular endothelial cells. These data demonstrate a previously unrecognized function of this pleiotropic cytokine: induction of monocyte migration into tissues. This function may be critical to the ability of MIF to promote diseases such as atherosclerosis and rheumatoid arthritis, in which macrophages are key participants.