12/15-Lipoxygenase deficiency protects mice from allergic airways inflammation and increases secretory IgA levels.
12/15-Lipoxygenase deficiency protects mice from allergic airways inflammation and increases secretory IgA levels.
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DOI：
10.1016/j.jaci.2008.06.021
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发表时间：
2008-09
影响因子：
14.2
通讯作者：
Kuperman, Douglas A.
中科院分区：
文献类型：
--
作者：
Hajek, Amanda R.;Lindley, Alexa R.;Favoreto, Silvio, Jr.;Carter, Roderick;Schleimer, Robert P.;Kuperman, Douglas A.
15-脂氧合酶-1（15-LO-1）的诱导已在哮喘患者的气道中观察到，尽管其在气道中的生理作用在很大程度上仍不明确。我们试图检验小鼠15-LO-1直系同源物12/15-LO有助于过敏性气道炎症的发展的假设。两种模型用于评估野生型和12/15-LO缺陷型小鼠。全身模型涉及腹腔注射过敏原，粘膜模型涉及过敏原暴露只发生在气道。通过比较两种模型中获得的结果，确定12/15-LO对过敏性致敏和气道炎症的全身和粘膜特异性贡献。在粘膜模型中，12/15-LO基因敲除小鼠受到保护，免受过敏性致敏和气道炎症的发展，如过敏原特异性IgE、IgG 1和IgG 2a的循环水平;支气管肺泡灌洗液中炎性细胞的特征;以及肺组织中细胞因子和介质的表达所证明的。在全身模型中，12/15-LO敲除小鼠未受到保护。这表明存在肺限制的12/15-LO缺乏症的保护作用，这可能是由粘膜B细胞的活化增加和已知的粘膜特异性保护介质分泌型伊加的产生增加引起的。在哮喘中诱导15-LO-1可能通过抑制分泌型伊加而导致过敏性致敏和气道炎症。
Induction of 15-lipoxygenase-1 (15-LO-1) has been observed in the airways of subjects with asthma, although its physiologic role in the airways has remained largely undefined. We sought to test the hypothesis that the mouse 15-LO-1 ortholog 12/15-LO contributes to the development of allergic airways inflammation. Two models were used to evaluate wild-type and 12/15-LO–deficient mice. The systemic model involved intraperitoneal injections of allergen, and the mucosal model involved allergen exposures occurring exclusively in the airways. The systemic and mucosal-specific contributions of 12/15-LO to allergic sensitization and airways inflammation were determined by comparing the results obtained in the 2 models. In the mucosal model 12/15-LO knockout mice were protected from the development of allergic sensitization and airways inflammation, as evidenced by circulating levels of allergen-specific IgE, IgG1, and IgG2a; the profile of inflammatory cells in bronchoalveolar lavage fluid; and the expression of cytokines and mediators in lung tissue. In the systemic model 12/15-LO knockout mice were not protected. This suggested the presence of a lung-restricted protective role for 12/15-LO deficiency that was potentially accounted for by increased activation of mucosal B cells and increased production of the known mucosal-specific protective mediator secretory IgA. Induction of 15-LO-1 in asthma might contribute to allergic sensitization and airways inflammation, potentially by causing suppression of secretory IgA.
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影响因子：
--
作者：
Kim N;Luster AD
通讯作者：
Luster AD
影响因子：
4.4
作者：
McCusker, Christine T.;Wang, Yufa;Fixman, Elizabeth D.
通讯作者：
Fixman, Elizabeth D.
DOI：
10.1016/j.bbrc.2005.08.029
发表时间：
2005-12-09
影响因子：
3.1
作者：
Jisaka, M;Iwanaga, C;Yokota, K
通讯作者：
Yokota, K
影响因子：
15.3
作者：
Middleton, Melissa Kristine;Zukas, Alicia Marie;Pure, Ellen
通讯作者：
Pure, Ellen
影响因子：
4.4
作者：
Kuperman, DA;Huang, XZ;Erle, DJ
通讯作者：
Erle, DJ