Pulmonary arterial remodeling induced by a Th2 immune response.
Pulmonary arterial remodeling induced by a Th2 immune response.
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DOI：
10.1084/jem.20071008
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发表时间：
2008-02-18
影响因子：
15.3
通讯作者：
Grunig, Gabriele
中科院分区：
文献类型：
--
作者：
Daley, Eleen;Emson, Claire;Guignabert, Christophe;Malefyt, Rene de Waal;Louten, Jennifer;Kurup, Viswanath P.;Hogaboam, Cory;Taraseviciene-Stewart, Laimute;Voelkel, Norbert F.;Rabinovitch, Marlene;Grunig, Ekkehard;Grunig, Gabriele
以血管平滑肌密度增加为特征的肺动脉重构是肺动脉高压（PAH）的常见病变，PAH是一种致命疾病。临床相关研究提示肺动脉重构的发生与免疫有关，但缺乏实验依据。我们表明，免疫接种和长期间歇性挑战，通过气道与两种不同的可溶性抗原诱导严重的肌化小到中型肺动脉。CD4+ T细胞、抗原特异性辅助性T细胞2型（Th2）反应或致病性Th2细胞因子白细胞介素13的耗竭显著改善了肺动脉肌化。肺动脉肌化的严重程度与表达平滑肌细胞有丝分裂原、抵抗素样分子α的上皮细胞和巨噬细胞数量增加相关，但令人惊讶的是，与肺动脉高压无关。我们的数据首次提供了实验证据，证明对可溶性抗原的适应性免疫应答足以引起严重的肺动脉肌化，并支持儿科患者和伴侣动物中的临床观察结果，即肌化代表可能共同导致PAH的肺动脉损伤事件之一。
Pulmonary arterial remodeling characterized by increased vascular smooth muscle density is a common lesion seen in pulmonary arterial hypertension (PAH), a deadly condition. Clinical correlation studies have suggested an immune pathogenesis of pulmonary arterial remodeling, but experimental proof has been lacking. We show that immunization and prolonged intermittent challenge via the airways with either of two different soluble antigens induced severe muscularization in small- to medium-sized pulmonary arteries. Depletion of CD4+ T cells, antigen-specific T helper type 2 (Th2) response, or the pathogenic Th2 cytokine interleukin 13 significantly ameliorated pulmonary arterial muscularization. The severity of pulmonary arterial muscularization was associated with increased numbers of epithelial cells and macrophages that expressed a smooth muscle cell mitogen, resistin-like molecule α, but surprisingly, there was no correlation with pulmonary hypertension. Our data are the first to provide experimental proof that the adaptive immune response to a soluble antigen is sufficient to cause severe pulmonary arterial muscularization, and support the clinical observations in pediatric patients and in companion animals that muscularization represents one of several injurious events to the pulmonary artery that may collectively contribute to PAH.
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影响因子：
6.4
作者：
CASLIN, AW;HEATH, D;SMITH, P
通讯作者：
SMITH, P
DOI：
10.1152/ajplung.00258.2006
发表时间：
2007-04-01
影响因子：
4.9
作者：
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通讯作者：
Klemm, Dwight J.
影响因子：
4.4
作者：
Ford, JG;Rennick, D;Grünig, G
通讯作者：
Grünig, G
影响因子：
4.6
作者：
Hoshikawa, Y;Nana-Sinkam, P;Geraci, MW
通讯作者：
Geraci, MW
影响因子：
5.9
作者：
ISERN, RA;YANEVA, M;ARNETT, FC
通讯作者：
ARNETT, FC