Eosinophil activation of fibroblasts from chronic allergen-induced disease utilizes stem cell factor for phenotypic changes
Eosinophil activation of fibroblasts from chronic allergen-induced disease utilizes stem cell factor for phenotypic changes
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DOI：
10.2353/ajpath.2008.070082
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发表时间：
2008-01-01
影响因子：
6
通讯作者：
Lukacs, Nicholas W.
中科院分区：
文献类型：
--
作者：
Dolgachev, Vladislav;Berlin, Aaron A.;Lukacs, Nicholas W.
在本研究中，研究了干细胞因子（SCF）在介导嗜酸性粒细胞和成纤维细胞相互作用过程中的作用。与正常小鼠的成纤维细胞相比，慢性过敏原小鼠肺部生长的成纤维细胞的 SCF 显着更高。当嗜酸性粒细胞沉积在过敏小鼠的成纤维细胞上时，与非过敏小鼠的成纤维细胞相比，检测到 SCF 显着增加。成纤维细胞与嗜酸性粒细胞的相互作用也增加了哮喘相关趋化因子 CCL5 和 CCL6 的产生，这种相互作用依赖于细胞与细胞之间的相互作用，并且仅在来自慢性过敏原攻击小鼠肺部的成纤维细胞中观察到，而在来自未受过敏原攻击的正常小鼠肺中的成纤维细胞中观察不到。当在嗜酸性粒细胞-成纤维细胞相互作用期间添加抗SCF抗体时，趋化因子的产生显着减少。来自慢性过敏原攻击小鼠的成纤维细胞与嗜酸性粒细胞的相互作用也增加了α-平滑肌细胞肌动蛋白和前胶原I的表达以及诱导的转化生长因子-β。肌成纤维细胞活化的变化依赖于 SCF 介导的途径，因为抗 SCF 抗体治疗减少了所有这三种后纤维化相关标志物的表达。因此，我们的数据表明，SCF 在慢性过敏反应期间介导成纤维细胞与招募的嗜酸性粒细胞相互作用的重要激活途径，并提示慢性疾病期间气道重塑的潜在机制。
in the present studies the role of stem cell factor (SCF) in mediating eosinophil and fibroblast activation during their interaction was investigated. SCF was significantly higher in fibroblasts grown from lungs of chronic allergen-challenged mice compared to fibroblasts grown from normal mice. When eosinophils were layered onto fibroblasts from allergic mice, a significant increase in SCF was detected compared to fibroblasts from nonallergic mice. The interaction of fibroblasts with eosinophils also increased the production of asthma-associated chemokines, CCL5 and CCL6, was dependent on cell-to-cell interaction, and was observed only with fibroblasts derived from lungs of chronic allergen-challenged mice and not from those derived from unchallenged normal mice. Chemokine production was significantly decreased when anti-SCF antibodies were added during eosinophil-fibroblast interaction. The interaction of fibroblasts from chronic allergen-challenged mice with eosinophils also increased a-smooth muscle cell actin and procollagen I expression as well as induced transforming growth factor-beta. The changes in myofibroblast activation were dependent on SCF-mediated pathways because anti-SCF antibody treatment reduced the expression of all three of these latter fibrosis-associated markers. Thus, our data suggest that SCF mediates an important activation pathway for fibroblasts during chronic allergic responses on interaction with recruited eosinophils and suggest a potential mechanism of airway remodeling during chronic disease.