Matrix regulation of lung injury, inflammation, and repair: the role of innate immunity.
Matrix regulation of lung injury, inflammation, and repair: the role of innate immunity.
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DOI：
10.1513/pats.200604-097aw
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发表时间：
2006-07-01
期刊：
影响因子：
--
通讯作者：
Jiang, Dianhua
中科院分区：
文献类型：
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作者：
Noble, Paul W;Jiang, Dianhua
非感染性组织损伤后调节宿主防御的机制尚不完全清楚。我们的实验室对细胞外基质糖胺聚糖透明质酸在肺炎症和纤维化调节中的作用感兴趣。我们已经确定了两个细胞表面受体系统的关键作用，与透明质酸相互作用，以控制肺部炎症和组织修复。造血CD44对于清除肺损伤后产生的透明质酸碎片是必要的。未能清除透明质酸碎片导致持续的炎症。然而，在缺乏CD44的情况下，肺泡巨噬细胞继续产生趋化因子以响应透明质酸片段，这暗示另一种受体系统控制巨噬细胞效应子功能。我们发现，Toll样受体2和4（TLR2和TLR4）是负责巨噬细胞炎症基因表达的透明质酸片段。尽管TLR2和TLR4在非感染性炎症中启动先天性免疫应答，但它们对肺泡上皮细胞的肺损伤具有保护作用。
Mechanisms that regulate host defense after noninfectious tissue injury are incompletely understood. Our laboratory is interested in the role of the extracellular matrix glycosaminoglycan hyaluronan in the regulation of lung inflammation and fibrosis. We have identified key roles for two cell surface receptor systems that interact with hyaluronan to control lung inflammation and tissue repair. Hematopoietic CD44 is necessary to clear hyaluronan fragments that are produced after lung injury. Failure to clear hyaluronan fragments leads to unremitting inflammation. However, in the absence of CD44, alveolar macrophages continue to produce chemokines in response to hyaluronan fragments, implicating another receptor system in controlling macrophage effector function. We found that Toll-like receptors 2 and 4 (TLR2 and TLR4) are responsible for macrophage inflammatory gene expression in response to hyaluronan fragments. Although TLR2 and TLR4 initiate the innate immune response in noninfectious inflammation, they have a protective role against lung injury on alveolar epithelial cells.