Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4.
Oligosaccharides of Hyaluronan activate dendritic cells via toll-like receptor 4.
复制标题
DOI：
10.1084/jem.20001858
复制
发表时间：
2002-01-07
期刊：
影响因子：
--
通讯作者：
Simon JC
中科院分区：
文献类型：
--
作者：
Termeer C;Benedix F;Sleeman J;Fieber C;Voith U;Ahrens T;Miyake K;Freudenberg M;Galanos C;Simon JC
炎症过程中产生的透明质酸 (sHA) 多糖的低分子量碎片产物已被证明是树突状细胞 (DC) 和巨噬细胞等免疫活性细胞的有效激活剂。在这里，我们报道 sHA 通过 Toll 样受体 (TLR)-4 诱导 DC 成熟，Toll 样受体 (TLR)-4 是一种与先天免疫和宿主针对细菌感染的防御相关的受体复合物。来自携带突变 TLR-4 等位基因的 C3H/HeJ 和 C57BL/10ScCr 小鼠的骨髓来源的 DC 对 sHA 诱导的表型和功能成熟无反应。相反，来自 TLR-2 缺陷小鼠的 DC 仍然对 sHA 敏感。相应地，向人单核细胞来源的 DC 中添加抗 TLR-4 mAb 可阻断 sHA 诱导的肿瘤坏死因子 α 的产生。蛋白质印迹分析显示，sHA 处理导致 p38/p42/44 MAP 激酶明显磷酸化和核因子 (NF)-κB（TLR-4 信号通路的所有组成部分）的核转位。通过特定抑制剂阻断该途径可完全消除 sHA 诱导的 DC 成熟。最后，静脉注射 sHA 诱导 DC 从皮肤迁移及其在脾脏中的表型和功能成熟，这同样取决于 TLR-4 的表达。总之，这是第一篇报道炎症过程中产生的细胞外基质的多糖降解产物可能作为 DC 上 TLR-4 复合物的内源配体。
Low molecular weight fragmentation products of the polysaccharide of Hyaluronic acid (sHA) produced during inflammation have been shown to be potent activators of immunocompetent cells such as dendritic cells (DCs) and macrophages. Here we report that sHA induces maturation of DCs via the Toll-like receptor (TLR)-4, a receptor complex associated with innate immunity and host defense against bacterial infection. Bone marrow–derived DCs from C3H/HeJ and C57BL/10ScCr mice carrying mutant TLR-4 alleles were nonresponsive to sHA-induced phenotypic and functional maturation. Conversely, DCs from TLR-2–deficient mice were still susceptible to sHA. In accordance, addition of an anti–TLR-4 mAb to human monocyte–derived DCs blocked sHA-induced tumor necrosis factor α production. Western blot analysis revealed that sHA treatment resulted in distinct phosphorylation of p38/p42/44 MAP-kinases and nuclear translocation of nuclear factor (NF)-κB, all components of the TLR-4 signaling pathway. Blockade of this pathway by specific inhibitors completely abrogated the sHA-induced DC maturation. Finally, intravenous injection of sHA-induced DC emigration from the skin and their phenotypic and functional maturation in the spleen, again depending on the expression of TLR-4. In conclusion, this is the first report that polysaccharide degradation products of the extracellular matrix produced during inflammation might serve as an endogenous ligand for the TLR-4 complex on DCs.
登录
查看更多内容
DOI：
10.1016/s0167-5699(98)01427-3
发表时间：
1999-05-01
期刊：
IMMUNOLOGY TODAY
影响因子：
--
作者：
Rescigno, M;Granucci, F;Ricciardi-Castagnoli, P
通讯作者：
Ricciardi-Castagnoli, P
DOI：
10.1073/pnas.90.7.3038
发表时间：
1993-04-01
影响因子：
11.1
作者：
INABA, K;INABA, M;STEINMAN, RM
通讯作者：
STEINMAN, RM
影响因子：
4.4
作者：
Ohashi, K;Burkart, V;Kolb, H
通讯作者：
Kolb, H
影响因子：
15.9
作者：
Lien, E;Means, TK;Golenbock, DT
通讯作者：
Golenbock, DT
影响因子：
4.8
作者：
ALESSI, DR;CUENDA, A;SALTIEL, AR
通讯作者：
SALTIEL, AR