Deficiency in the serum-derived hyaluronan-associated protein-hyaluronan complex enhances airway hyperresponsiveness in a murine model of asthma.
Deficiency in the serum-derived hyaluronan-associated protein-hyaluronan complex enhances airway hyperresponsiveness in a murine model of asthma.
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血清来源的乙酰透明质酸相关蛋白-乙酰透明质酸复合物的缺乏会增强小鼠哮喘模型中的气道高反应性。
DOI：
10.1159/000314362
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发表时间：
2010
影响因子：
2.8
通讯作者：
Baba,Kenji
中科院分区：
文献类型：
--
作者：
Zhu,Long;Zhuo,Lisheng;Kimata,Koji;Yamaguchi,Etsuro;Watanabe,Hideto;Aronica,MarkA;Hascall,VincentC;Baba,Kenji
背景血清源性透明质酸（HA）相关蛋白（SHAP）是α-胰蛋白酶间抑制剂的重链，与HA共价结合形成SHAP-HA复合物。SHAP-HA复合物参与炎性疾病（包括类风湿性关节炎）的病理生理学。我们调查是否这个复杂的也参与了气道allergy.MethodsSHAP-HA缺陷型（bikunin敲除，KO）小鼠和野生型（WT）小鼠免疫两次，通过腹腔注射卵清蛋白（OVA）和暴露于气雾剂OVA 30分钟，每天2周。24小时后，最后的OVA的挑战，气道反应性吸入乙酰甲胆碱（MCh）进行了测量，并分析支气管肺泡灌洗液（BALF）和肺组织学studies.ResultsCompared WT小鼠，KO小鼠表现出较高的气道高反应性吸入MCh和较高的晚期反应，而早期反应是相似的。BALF细胞分化显示KO小鼠中巨噬细胞和中性粒细胞数量增加。此外，KO小鼠BALF中可溶性肿瘤坏死因子受体1（sTNFR 1）浓度降低，而Th 1和Th 2细胞因子水平与WT小鼠无差异。肺组织的免疫化学研究显示，在KO比在WT mice.ConclusionsOur结果表明，在这个小鼠哮喘模型中，SHAP-HA复合物具有抑制作用的气道高反应性和过敏性气道炎症的发展，这可能是由于，至少部分，负反馈机制施加的sTNFR 1，SHAP-HA复合物也可促进其从细胞表面脱落。
BackgroundSerum-derived hyaluronan (HA)-associated proteins (SHAPs), the heavy chains of inter-α-trypsin inhibitor, covalently bind to HA to form the SHAP-HA complex. The SHAP-HA complex is involved in the pathophysiology of inflammatory diseases, including rheumatoid arthritis. We investigated whether this complex is also involved in airway allergy.MethodsSHAP-HA-deficient (bikunin knockout, KO) mice and wild-type (WT) mice were immunized twice by intraperitoneal injection of ovalbumin (OVA) and exposed to aerosol OVA for 30 min each day for 2 weeks. Twenty-four hours after the final OVA challenge, airway responsiveness to inhaled methacholine (MCh) was measured, and analysis of bronchoalveolar lavage fluid (BALF) and lung histological studies were done.ResultsCompared to WT mice, KO mice showed higher airway hyperresponsiveness to inhaled MCh and higher late-phase responses to OVA whereas the early-phase responses were similar. Cell differentials of BALF showed an increased number of macrophages and neutrophils in KO mice. Furthermore, decreased concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1) were found in BALF from KO mice whereas the levels of Th1 and Th2 cytokines were not different from WT mice. Immunochemical study of the lung tissues revealed stronger staining of sTNFR1 in KO than in WT mice.ConclusionsOur results suggest that in this murine asthma model, the SHAP-HA complex has an inhibitory role in the development of airway hyperresponsiveness and allergic airway inflammation which may be attributed, at least in part, to negative feedback mechanisms exerted by sTNFR1, the shedding of which from the cell surface might also be promoted by the SHAP-HA complex.