Transgenic expression of human S100A12 induces structural airway abnormalities and limited lung inflammation in a mouse model of allergic inflammation.
Transgenic expression of human S100A12 induces structural airway abnormalities and limited lung inflammation in a mouse model of allergic inflammation.
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DOI：
10.1111/j.1365-2222.2011.03714.x
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
Camoretti-Mercado B
中科院分区：
文献类型：
--
作者：
Hofmann Bowman MA;Heydemann A;Gawdzik J;Shilling RA;Camoretti-Mercado B
钙结合蛋白S100A12在过敏性哮喘患者的血清和痰中高度表达，可能是哮喘的生物标志物和病理介质。目的：检测S100A12在过敏性肺炎小鼠模型中介导呼吸道炎症的作用。表达人S100A12和野生型窝窝子的转基因小鼠被卵蛋白致敏和攻击，并评估炎症、肺结构和功能。在卵蛋白致敏和激发后，与野生型致敏和激发的动物相比，S100A12转基因小鼠的支气管和血管周围炎症、粘液产生和嗜酸性粒细胞减少，对收缩激动剂的呼吸道反应性减弱。这至少部分可以通过S100A12转基因小鼠的呼吸道改建来解释，这些小鼠的气道平滑肌变薄。S100A12可诱导培养的小鼠气道平滑肌细胞Fas表达和caspase3的活化，提示S100A12转基因小鼠的气道平滑肌异常可能是通过心肌细胞凋亡来实现的。S100A12是在人类哮喘患者呼吸道中发现的含量最丰富的蛋白质之一，推测S100A12可能参与了炎症过程。我们的研究首次表明，在卵蛋白诱导的过敏性炎症模型中，S100A12在小鼠肺中的转基因表达不会加剧肺部炎症。我们推测，在哮喘患者和卵清蛋白处理的转基因S100A12小鼠的BALF中发现的高水平的S100/钙颗粒蛋白并不显著地介导肺部炎症。
The calcium binding protein S100A12 is highly upregulated in the serum and sputum of patients with allergic asthma and is suggested to be a biomarker and pathologic mediator of asthma. To test the role of S100A12 in mediating airway inflammation in a mouse model of allergic lung inflammation. Transgenic mice that express human S100A12 and wild type littermates were sensitized and challenged with ovalbumin and assessed for inflammation, lung structure and function. Following ovalbumin sensitization and challenge, S100A12 transgenic mice showed reduced peribronchial and perivascular inflammation, mucus production and eosinophilia as well as attenuated airway responsiveness to contractile agonist compared to wild type sensitized and challenged animals. This is explained, at least in part, by remodeled airways in S100A12 transgenic mice with thinning of the airway smooth muscle. S100A12 exposure induced Fas expression and activation of caspase 3 in cultured airway smooth muscle cells, suggesting that airway smooth muscle abnormalities observed in S100A12 transgenic mice may be mediated through myocyte apoptosis. S100A12 is one of the most abundant proteins found in the airways of human asthmatics, and it was postulated that S100A12 could mediate the inflammatory process. Our study shows for the first time that transgenic expression of S100A12 in the lung of mice does not exacerbate lung inflammation in a model of ovalbumin-induced allergic inflammation. We speculate that the high levels of S100/calgranulins found in BALF of asthmatics and of ovalbumin-treated transgenic S100A12 mice do not significantly mediate pulmonary inflammation.
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影响因子：
20.1
作者：
Hofmann Bowman M;Wilk J;Heydemann A;Kim G;Rehman J;Lodato JA;Raman J;McNally EM
通讯作者：
McNally EM
影响因子：
15.9
作者：
Harja, Evis;Bu, De-Xiu;Schmidt, Ann Marie
通讯作者：
Schmidt, Ann Marie
影响因子：
3.4
作者：
Calvo, Florence Quesada;Fillet, Marianne;Cataldo, Didier
通讯作者：
Cataldo, Didier
影响因子：
4
作者：
Kumar, RK;Foster, PS
通讯作者：
Foster, PS
影响因子：
30.8
作者：
Cookson, WOCM;Ubhi, B;Harper, JI
通讯作者：
Harper, JI