Nascent Endothelium Initiates Th2 Polarization of Asthma
Nascent Endothelium Initiates Th2 Polarization of Asthma
复制标题
DOI：
10.4049/jimmunol.1202095
复制
发表时间：
2013-04-01
影响因子：
4.4
通讯作者：
Erzurum, Serpil C.
中科院分区：
文献类型：
--
作者：
Asosingh, Kewal;Cheng, Georgiana;Erzurum, Serpil C.
哮喘气道重塑与Th2炎症有关。血管生成是气道重构的一贯特征，但其病理生理作用尚不清楚。我们假设新生血管中的内皮细胞足以引发th2炎症。血管内皮(VE)-钙粘蛋白是一种组成性表达的内皮细胞粘附分子，在粘附连接形成之前以单体形式暴露在内皮尖细胞上。靶向ve -钙粘蛋白单体的抗体通过阻断这种粘附连接的形成来抑制血管生成。在这项研究中，ve -钙粘蛋白单体Ab减少了过敏原诱导的小鼠哮喘模型肺部的血管生成。引人注目的是，通过VE-cadherin阻断抑制内皮IL-25和促血管生成祖细胞胸腺基质淋巴生成素产生的机制，包括IgE产生、气道嗜酸性粒细胞浸润、上皮下纤维化、粘液化生和气道高反应性在内的Th2反应也被减弱。结果确定血管生成反应在特应性炎症的起源。免疫学杂志，2013,29(1):357 - 357。
Asthma airway remodeling is linked to Th2 inflammation. Angiogenesis is a consistent feature of airway remodeling, but its contribution to pathophysiology remains unclear. We hypothesized that nascent endothelial cells in newly forming vessels are sufficient to initiate Th2-inflammation. Vascular endothelial (VE)-cadherin is a constitutively expressed endothelial cell adhesion molecule that is exposed in its monomer form on endothelial tip cells prior to adherens junction formation. Abs targeted to VE-cadherin monomers inhibit angiogenesis by blocking this adherens junction formation. In this study, VE-cadherin monomer Ab reduced angiogenesis in the lungs of the allergen-induced murine asthma model. Strikingly, Th2 responses including, IgE production, eosinophil infiltration of the airway, subepithelial fibrosis, mucus metaplasia, and airway-hyperreactivity were also attenuated by VE-cadherin blockade, via mechanisms that blunted endothelial IL-25 and proangiogenic progenitor cell thymic stromal lymphopoietin production. The results identify angiogenic responses in the origins of atopic inflammation. The Journal of Immunology, 2013, 190: 3458-3465.