Macrophage migration inhibitory factor is critical to interleukin-5-driven eosinophilopoiesis and tissue eosinophilia triggered by Schistosoma mansoni infection
Macrophage migration inhibitory factor is critical to interleukin-5-driven eosinophilopoiesis and tissue eosinophilia triggered by Schistosoma mansoni infection
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DOI：
10.1096/fj.08-124248
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发表时间：
2009-04-01
期刊：
影响因子：
4.8
通讯作者：
Bozza, Marcelo T.
中科院分区：
文献类型：
--
作者：
Magalhaes, Elizabeth S.;Paiva, Claudia N.;Bozza, Marcelo T.
巨噬细胞移动抑制因子（MIF）参与炎症性疾病的发病机制，包括哮喘，其中它增强气道超敏反应和组织嗜酸性粒细胞增多。在此，我们研究了MIF的作用，嗜酸性粒细胞和组织嗜酸性粒细胞使用曼氏血吸虫感染。与野生型小鼠相比，MIF缺陷型（Mif（-/-））小鼠具有相似数量的蠕虫、虫卵和肉芽肿，但由于嗜酸性粒细胞数量较少，肉芽肿的大小显著减小。MIF不影响获得性感染反应，因为Mif（-/-）小鼠产生正常量的Th 2细胞因子和IgE。然而，重组MIF（rMIF）表现为嗜酸性粒细胞的化学引诱物，这可以部分解释感染的Mif（-/-）小鼠中嗜酸性粒细胞减少。Mif（-/-）小鼠慢性感染S. mansoni与野生型相比。Mif（-/-）对白细胞介素（IL）-5的应答中有损害的嗜酸性粒细胞生成，并且将rMIF添加到来自IL-5转基因小鼠的骨髓培养物中增强了嗜酸性粒细胞的生成。在缺乏MIF的情况下，嗜酸性粒细胞前体不能在补充IL-5的细胞培养物中存活，并被巨噬细胞摄取。用pancaspase抑制剂z-VAD或rMIF处理促进嗜酸性粒细胞祖细胞的存活。总之，这些结果表明，MIF参与IL-5驱动的嗜酸性粒细胞成熟和与S。曼氏感染Magalhaes，E.美国，派瓦角N.，Souza，H. S. P.，Pyrrho，A.美国，Mourao-Sa，D.，菲格雷多河T.，Vieira-de-Abreu，A.，Dutra，H.美国，Silveira，M.美国，Gaspar-Elsas，M. I. C.的方法，Xavier-Elsas，P.，Bozza，P. T.，博扎湾T.巨噬细胞移动抑制因子对IL-5驱动的嗜酸性粒细胞生成和曼氏血吸虫感染引发的组织嗜酸性粒细胞增多至关重要。FASEB J. 23，1262-1271（2009）
Macrophage migration inhibitory factor (MIF) participates in the pathogenesis of inflammatory diseases, including asthma, in which it enhances airway hypersensitivity and tissue eosinophilia. Herein, we investigated the role of MIF in eosinophilopoiesis and tissue eosinophilia using Schistosoma mansoni infection. MIF-deficient (Mif(-/-)) mice had similar numbers of adult worms, eggs, and granulomas compared to wildtype mice, but the size of granulomas was strikingly reduced due to smaller numbers of eosinophils. MIF did not affect the acquired response to infection, as Mif(-/-) mice produced normal amounts of Th2 cytokines and IgE. Nevertheless, recombinant MIF (rMIF) behaved as a chemoattractant for eosinophils, what could partially explain the reduced eosinophilia in infected Mif(-/-) mice. Moreover, the percentage of eosinophils was reduced in bone marrows of Mif(-/-) mice chronically infected with S. mansoni compared to wild type. Mif(-/-) had impaired eosinophilopoiesis in response to interleukin (IL)-5 and addition of rMIF to bone marrow cultures from IL-5 transgenic mice enhanced the generation of eosinophils. In the absence of MIF, eosinophil precursors were unable to survive the IL-5-supplemented cell culture, and were ingested by macrophages. Treatment with pancaspase inhibitor z-VAD or rMIF promoted the survival of eosinophil progenitors. Together, these results indicate that MIF participates in IL-5-driven maturation of eosinophils and in tissue eosinophilia associated with S. mansoni infection.-Magalhaes, E. S., Paiva, C. N., Souza, H. S. P., Pyrrho, A. S., Mourao-Sa, D., Figueiredo, R. T., Vieira-de-Abreu, A., Dutra, H. S., Silveira, M. S., Gaspar-Elsas, M. I. C., Xavier-Elsas, P., Bozza, P. T., Bozza, M. T. Macrophage migration inhibitory factor is critical to IL-5-driven eosinophilopoiesis and tissue eosinophilia triggered by Schistosoma mansoni infection. FASEB J. 23, 1262-1271 (2009)