A severe deficiency of coagulation factor VIIa results in attenuation of the asthmatic response in mice.
A severe deficiency of coagulation factor VIIa results in attenuation of the asthmatic response in mice.
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严重缺乏凝血因子 VIIa 会导致小鼠哮喘反应减弱。
DOI：
10.1152/ajplung.90638.2008
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Castellino,FrancisJ
中科院分区：
文献类型：
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作者：
Shinagawa,Kazuhiko;Ploplis,VictoriaA;Castellino,FrancisJ
卵清蛋白（OVA）激发后，野生型（WT）小鼠支气管肺泡灌洗液中的嗜酸性粒细胞计数增加，而OVA激发的低表达凝血因子VII（FVIItTA/tTA）小鼠的反应则减弱。辅助性T细胞2型（Th 2）细胞因子IL-4、IL-5和IL-13以及嗜酸性粒细胞吸引趋化因子eotaxin和RANTES的水平在OVA攻击的FVIItTA/tTAmice中也较低。与WT嗜酸性粒细胞相比，从低FVII小鼠纯化的嗜酸性粒细胞以更快的速率经历凋亡，并且在从FVIItTA/tTAmice获得的嗜酸性粒细胞中，响应于嗜酸性粒细胞活化趋化因子的嗜酸性粒细胞迁移减少。在OVA处理的FVIItTA/tTAmice中，气道高反应性和粘膜层厚度降低，并且外源性凝血因子X（FX）的添加增强了人上皮NCI-H292细胞中的粘蛋白产生。相应地，FX与NCI-H292细胞的孵育导致活化的（a）FX产生，表明FX活化所需的组分存在于NCI-H292细胞上。这些结果表明，FVIIa通过刺激肺嗜酸性粒细胞增多、气道高反应性和粘蛋白产生而在对变应原的哮喘反应中起作用，后者的作用是通过其与组织因子一起激活FX的能力。
Eosinophil counts in the bronchoalveolar lavage fluid of wild-type (WT) mice increased after ovalbumin (OVA) challenge, a response that was diminished in comparably challenged low-expressing coagulation factor VII (FVIItTA/tTA) mice. Levels of T helper type 2 (Th2) cytokines, IL-4, IL-5, and IL-13, and eosinophil-attracting chemokines, eotaxin and RANTES, were also lower in the OVA-challenged FVIItTA/tTAmice. Eosinophils purified from low-FVII mice underwent apoptosis at a faster rate compared with WT eosinophils, and eosinophil migration in response to eotaxin was reduced in eosinophils obtained from FVIItTA/tTAmice. Airway hyperresponsiveness and mucous layer thickness were reduced in OVA-treated FVIItTA/tTAmice, and addition of exogenous coagulation factor X (FX) enhanced mucin production in human epithelial NCI-H292 cells. Correspondingly, incubation of FX with NCI-H292 cells resulted in activated (a) FX production, suggesting that the components required for FX activation were present on NCI-H292 cells. These results demonstrate that FVIIa functions in the asthmatic response to an allergen by stimulating lung eosinophilia, airway hyperresponsiveness, and mucin production, this latter effect through its ability to activate FX in conjunction with tissue factor.