Protection of plasminogen activator inhibitor-1-deficient mice from nasal allergy
Protection of plasminogen activator inhibitor-1-deficient mice from nasal allergy
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DOI：
10.4049/jimmunol.174.12.8135
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发表时间：
2005-06-15
影响因子：
4.4
通讯作者：
Sakata, Y
中科院分区：
文献类型：
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作者：
Sejima, T;Madoiwa, S;Sakata, Y
本研究旨在阐明纤维蛋白溶解成分与过敏病理之间的关系，特别是在鼻腔过敏和鼻腔组织改变的发展过程中。在野生型（WT） C57BL/6J小鼠中，经口服OVA致敏后鼻内OVA刺激诱导的上皮下胶原沉积水平高于纤溶酶原激活物抑制剂(PAI)-1缺陷（PAI-1(-/-)）小鼠。与wt对照组小鼠相比，WT-OVA小鼠鼻黏膜中PAI-1诱导水平过高，鼻灌洗液中PAI-1活性水平升高，表明蛋白水解活性的降低抑制了上皮下胶原蛋白的去除。WT-OVA小鼠打喷嚏、擦鼻频率、鼻高反应性、血清中特异性IgG1和IgE的产生以及脾细胞培养上清中IL-4和IL-5的产生均显著升高。在PAI-1（-/-）小鼠中，这些反应不存在，血清中特异性IgG2a和脾细胞培养基中ifn - γ显著升高。病理组织学上，WT-OVA小鼠鼻黏膜可见明显的杯状细胞增生和嗜酸性粒细胞浸润，而PAI-1（-/-）小鼠鼻黏膜未见此现象。这些结果表明，WT-OVA小鼠的免疫反应可归类为显性Th2反应，Th2反应会促进胶原沉积。相比之下，PAI-1（-/-）小鼠的Th2反应下调，免疫反应从Th2优势反应转变为th1优势反应。综上所述，这些发现表明PAI-1不仅在溶栓中起重要作用，而且在免疫应答中也起重要作用。
This study was performed to clarify the relationship between fibrinolytic components and the pathology of allergy, particularly that during the development of nasal allergy and nasal tissue changes. Intranasal OVA challenge after sensitization by i.p. administration of OVA induced a higher level of excess subepithelial collagen deposition in wild-type (WT) C57BL/6J mice than in plasminogen activator inhibitor (PAI)-1-deficient (PAI-1(-/-)) mice. The excess PAI-1 induction in the nasal mucosa and higher level of active PAI-1 in the nasal lavage fluid of WT-OVA mice compared with those in WT-control mice suggested that the decrease of proteolytic activity inhibits the removal of subepithelial collagen. The frequency of sneezing, nasal rubbing, nasal hyperresponsiveness, production of specific IgG1 and IgE in the serum, and production of IL-4 and IL-5 in splenocyte culture supernatant increased significantly in WT-OVA mice. In PAI-1(-/-) mice, these reactions were absent, and specific IgG2a in serum and IFN-gamma in splenocyte culture medium increased significantly. Histopathologically, there were marked goblet cell hyperplasia and eosinophil infiltration into the nasal mucosa in WT-OVA mice, but these were absent in PAI-1(-/-) mice. These results indicate that the immune response in WT-OVA mice can be classified as a dominant Th2 response, which would promote collagen deposition. In contrast, the Th2 response in PAI-1(-/-) mice was down-regulated, and the immune response shifted from Th2-dominant reaction to a Th1-dominant one. Taken together, these findings suggest that PAI-1 plays an important role not only in thrombolysis but also in immune response.