Serum amyloid P inhibits fibrosis through Fc gamma R-dependent monocyte-macrophage regulation in vivo.
Serum amyloid P inhibits fibrosis through Fc gamma R-dependent monocyte-macrophage regulation in vivo.
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DOI：
10.1126/scitranslmed.3000111
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发表时间：
2009-11-04
影响因子：
17.1
通讯作者：
Duffield JS
中科院分区：
文献类型：
--
作者：
Castaño AP;Lin SL;Surowy T;Nowlin BT;Turlapati SA;Patel T;Singh A;Li S;Lupher ML Jr;Duffield JS
迫切需要针对慢性炎症伴纤维化的新疗法。越来越多的证据表明，炎症细胞的先天激活驱动慢性器官纤维化。血清淀粉样蛋白P是一种天然循环的可溶性模式识别受体，是五聚蛋白家族的成员。它将Fc γ相关分子模式识别与Fcγ受体介导的吞噬作用联系起来。在此，我们发现，治疗性给予人血清淀粉样蛋白P可显著抑制小鼠肾脏中的纤维化进展，通过激活Fcγ受体进行调节，并依赖于炎性单核细胞和巨噬细胞，但不依赖于纤维细胞。人血清淀粉样蛋白P介导的小鼠肾纤维化抑制与人血清淀粉样蛋白P与细胞碎片的特异性结合以及随后在体外和体内对炎性单核细胞和肾巨噬细胞的抑制相关，并且依赖于与活化Fcγ受体和白细胞介素-10表达的调节结合。这些研究揭示了Fcγ受体在无菌性炎症中的作用，并强调血清淀粉样蛋白P通过局部产生白细胞介素-10作为潜在的抗纤维化治疗。
New therapies that target chronic inflammation with fibrosis are urgently required. Increasing evidence points to innate activation of inflammatory cells in driving chronic organ fibrosis. Serum amyloid P is a naturally circulating soluble pattern recognition receptor, a member of the family of pentraxin proteins. It links danger-associated molecular pattern recognition to Fcγ receptor–mediated phagocytosis. Here we show that fibrosis progression in the mouse kidney is significantly inhibited by therapeutic administration of human serum amyloid P, regulated by activating Fcγ receptors, and dependent on inflammatory monocytes and macrophages, but not fibrocytes. Human serum amyloid P–mediated inhibition of mouse kidney fibrosis correlated with specific binding of human serum amyloid P to cell debris and with subsequent suppression of inflammatory monocytes and kidney macrophages in vitro and in vivo, and was dependent on regulated binding to activating Fcγ receptors and interleukin-10 expression. These studies uncover previously unidentified roles for Fcγ receptors in sterile inflammation and highlight serum amyloid P as a potential antifibrotic therapy through local generation of interleukin-10.
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影响因子：
56.9
作者：
MADRENAS, J;WANGE, RL;GERMAIN, RN
通讯作者：
GERMAIN, RN
影响因子：
4.3
作者：
Ciurana, Caroline L. F.;Hack, C. Erik
通讯作者：
Hack, C. Erik
影响因子：
6
作者：
Lin, Shuei-Liong;Kisseleva, Tatiana;Duffield, Jeremy S.
通讯作者：
Duffield, Jeremy S.
影响因子：
15.9
作者：
Duffield, JS;Forbes, SJ;Iredale, JP
通讯作者：
Iredale, JP
DOI：
10.1073/pnas.0804910105
发表时间：
2008-07-22
影响因子：
11.1
作者：
Haudek, Sandra B.;Trial, JoAnn;Entman, Mark L.
通讯作者：
Entman, Mark L.