S100A4(+) Macrophages Are Necessary for Pulmonary Fibrosis by Activating Lung Fibroblasts.
S100A4(+) Macrophages Are Necessary for Pulmonary Fibrosis by Activating Lung Fibroblasts.
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S100A4( ) 巨噬细胞通过激活肺成纤维细胞是肺纤维化所必需的
DOI：
10.3389/fimmu.2018.01776
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发表时间：
2018
影响因子：
7.3
通讯作者：
Qin Z
中科院分区：
文献类型：
--
作者：
Li Y;Bao J;Bian Y;Erben U;Wang P;Song K;Liu S;Li Z;Gao Z;Qin Z
S100A4是一种钙结合蛋白，可通过成纤维细胞活化促进肺纤维化。部分由于其不同的细胞起源，S100A4在肺纤维化发展中的确切作用仍然难以捉摸。本研究表明，在支气管肺泡灌洗液中，S100A4+巨噬细胞的数量与S100A4蛋白水平和患者特发性肺纤维化（IPF）的发生密切相关。博莱霉素诱导肺纤维化小鼠模型显示，炎症期细胞外S100A4主要来源于S100A4+巨噬细胞。体外研究表明，细胞外S100A4可通过上调α-SMA和I型胶原蛋白激活小鼠和人肺成纤维细胞，并使鞘氨醇-1-磷酸（S1P）升高。抑制S1P受体亚型S1P1/S1P3可消除成纤维细胞的激活。因此，体内缺乏或中和S100A4可显著减轻博莱霉素诱导的肺纤维化。重要的是，S100A4+而非S100A4 -巨噬细胞的过继性转移在对纤维化诱导不敏感的S100A4 - / -小鼠中造成实验性肺损伤。综上所述，巨噬细胞释放的S100A4通过激活与S1P相关的肺成纤维细胞来促进肺纤维化。这表明肺内细胞外S100A4或S100A4+巨噬细胞是IPF早期临床诊断或治疗的有希望的靶点。
S100A4, a calcium-binding protein, can promote pulmonary fibrosis via fibroblast activation. Due partly to its various cellular origins, the exact role of S100A4 in the development of lung fibrosis remains elusive. Here, we show that in the bronchoalveolar lavage fluid, numbers of S100A4+ macrophages correlated well with S100A4 protein levels and occurrence of idiopathic pulmonary fibrosis (IPF) in patients. A mouse model of bleomycin-induced pulmonary fibrosis demonstrated S100A4+ macrophages as main source for extracellular S100A4 in the inflammatory phase. In vitro studies revealed that extracellular S100A4 could activate both mouse and human lung fibroblasts by upregulation of α-SMA and type I collagen, during which sphingosine-1-phosphate (S1P) increased. Inhibiting the S1P receptor subtypes S1P1/S1P3 abrogated fibroblast activation. Accordingly, absence or neutralization of S100A4 significantly attenuated bleomycin-induced lung fibrosis in vivo. Importantly, adoptive transfer of S100A4+ but not of S100A4− macrophages installed experimental lung injury in S100A4−/− mice that were otherwise not sensitive to fibrosis induction. Taken together, S100A4 released by macrophages promotes pulmonary fibrosis through activation of lung fibroblasts which is associated with S1P. This suggests that extracellular S100A4 or S100A4+ macrophages within the lung as promising targets for early clinical diagnosis or therapy of IPF.
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S100A4 通过 TLR4-ERK1/2 信号传导保护骨髓源性抑制细胞免遭内源性凋亡
影响因子：
7.3
作者：
Li Q;Dai C;Xue R;Wang P;Chen L;Han Y;Erben U;Qin Z
通讯作者：
Qin Z
影响因子：
3.7
作者：
Björk P;Källberg E;Wellmar U;Riva M;Olsson A;He Z;Törngren M;Liberg D;Ivars F;Leanderson T
通讯作者：
Leanderson T
DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1164/rccm.200402-147oc
发表时间：
2004-10-15
影响因子：
24.7
作者：
Flaherty, KR;King, TE;Martinez, FJ
通讯作者：
Martinez, FJ
影响因子：
15.9
作者：
Hashimoto, N;Jin, H;Phan, SH
通讯作者：
Phan, SH