Role of hyaluronan and hyaluronan-binding proteins in human asthma.
Role of hyaluronan and hyaluronan-binding proteins in human asthma.
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DOI：
10.1016/j.jaci.2011.04.006
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Noble PW
中科院分区：
文献类型：
--
作者：
Liang J;Jiang D;Jung Y;Xie T;Ingram J;Church T;Degan S;Leonard M;Kraft M;Noble PW
人类哮喘的特征是慢性炎症和气道重塑。透明质酸（HA）是一种主要的细胞外基质成分，在包括哮喘在内的炎症性肺部疾病中积累。Hybryonan片段刺激巨噬细胞产生炎性细胞因子。我们假设HA及其受体在人类哮喘中发挥作用。探讨HA及其结合蛋白在哮喘发病中的作用。21例哮喘患者和25例正常对照者接受了支气管镜检查、支气管内活检和支气管肺泡灌洗（BAL）。培养成纤维细胞，在基线和暴露于与哮喘病理生物学相关的几种介质后测定HA和HA合酶表达。流式细胞术检测BAL巨噬细胞表面HA结合蛋白、CD 44、TLR 2和TLR 4的表达。比较了响应于HA片段刺激的巨噬细胞的IL-8产生。与正常成纤维细胞相比，哮喘患者的气道成纤维细胞产生的低分子量HA浓度显著增加。在哮喘成纤维细胞中，Hybryonan synthase 2 mRNA表达明显增加。哮喘巨噬细胞显示细胞表面CD 44表达减少，TLR 2和TLR 4表达增加。哮喘受试者的巨噬细胞对低分子量HA刺激的反应性增加，如IL-8产生增加所示。哮喘患者HA稳态紊乱，成纤维细胞HA生成增加，肺泡巨噬细胞CD 44表达减少。对HA片段敏感性增加的巨噬细胞上TLR 2和TLR 4的上调表明了一种新的促炎机制，HA片段的持续存在可能有助于哮喘中的慢性炎症和气道重塑。
The characteristics of human asthma are chronic inflammation and airway remodeling. Hyaluronan (HA), a major extracellular matrix component, accumulates during inflammatory lung diseases including asthma. Hyaluronan fragments stimulate macrophages to produce inflammatory cytokines. We hypothesized that HA and its receptors would play a role in human asthma. To investigate the role of HA and HA binding proteins in human asthma. Twenty-one subjects with asthma and 25 normal control subjects underwent bronchoscopy with endobronchial biopsy and bronchoalveolar lavage (BAL). Fibroblasts were cultured, HA and HA synthase expression was determined at baseline and after exposure to several mediators relevant to asthma pathobiology. The expression of HA binding proteins, CD44, TLR2 and TLR4 on BAL macrophages was determined by flow cytometry. IL-8 production by macrophages in response to HA fragment stimulation was compared. Airway fibroblasts from asthma patients produced significantly increased concentrations of lower molecular weight HA compared to those of normal fibroblasts. Hyaluronan synthase 2 mRNA was markedly increased in asthmatic fibroblasts. Asthmatic macrophages showed a decrease in cell surface CD44 expression and an increase in TLR2 and TLR4 expression. Macrophages from asthmatic subjects showed an increase in responsiveness to low molecular weight HA stimulation, as demonstrated by increased IL-8 production. HA homeostasis is deranged in asthma with increased production by fibroblasts and decreased CD44 expression on alveolar macrophages. Upregulation of TLR2 and TLR4 on macrophages with increased sensitivity to HA fragments suggests a novel pro-inflammatory mechanism by which persistence of HA fragments could contribute to chronic inflammation and airway remodeling in asthma.
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发表时间：
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影响因子：
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作者：
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