Mesenchymal Stem Cells Inhibit Complement Activation by Secreting Factor H
Mesenchymal Stem Cells Inhibit Complement Activation by Secreting Factor H
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DOI：
10.1089/scd.2009.0418
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发表时间：
2010-11-01
影响因子：
4
通讯作者：
Lin, Feng
中科院分区：
文献类型：
--
作者：
Tu, Zhidan;Li, Qing;Lin, Feng
间充质干细胞（MSC）具有强大而广泛的免疫抑制能力，并已在治疗许多炎症性疾病的临床试验中显示出前景。以往的研究发现，MSCs在获得性免疫中抑制树突状细胞、T细胞和B细胞的活性，但MSCs是否在先天性免疫中抑制补体活性，以及其作用机制尚不明确。在这份报告中，我们发现，骨髓间充质干细胞组成性分泌H因子，这有力地抑制补体激活。MSC条件无血清培养基中因子H的耗尽消除了它们的补体抑制活性。此外，炎症细胞因子TNF-α和干扰素-γ（IFN-γ）以剂量和时间依赖性方式增强MSC产生因子H，而IL-6没有显著影响。此外，MSC的因子H产生被前列腺素E2（PGE 2）合成抑制剂吲哚美辛和吲哚胺2，3-双加氧酶（IDO）抑制剂1-甲基-D-色氨酸（1-MT）显著抑制，已知这两种抑制剂都有效地抑制MSC的免疫抑制活性。这些结果表明，MSC通过产生因子H抑制补体激活，这可能是MSC广泛免疫抑制能力的另一种机制。
Mesenchymal stem cells (MSCs) possess potent and broad immunosuppressive capabilities, and have shown promise in clinical trials treating many inflammatory diseases. Previous studies have found that MSCs inhibit dendritic cell, T-cell, and B-cell activities in the adaptive immunity; however, whether MSCs inhibit complement in the innate immunity, and if so, by which mechanism, have not been established. In this report, we found that MSCs constitutively secrete factor H, which potently inhibits complement activation. Depletion of factor H in the MSC-conditioned serum-free media abolishes their complement inhibitory activities. In addition, production of factor H by MSCs is augmented by inflammatory cytokines TNF-alpha and interferon-gamma (IFN-gamma) in dose-and time-dependent manners, while IL-6 does not have a significant effect. Furthermore, the factor H production from MSCs is significantly suppressed by the prostaglandin E2 (PGE2) synthesis inhibitor indomethacin and the indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyl-D-tryptophan (1-MT), both of which inhibitors are known to efficiently dampen MSCs immunosuppressive activity. These results indicate that MSCs inhibit complement activation by producing factor H, which could be another mechanism underlying MSCs broad immunosuppressive capabilities.