Analysis of bone-marrow derived fibroblasts involved in asthmatic airway remodeling and its interventional control of function

骨髓成纤维细胞参与哮喘气道重塑及其功能介入控制的分析

• 批准号: 17590802
• 负责人: YAMAUCHI Kohei
• 金额: $ 2.24万
• 依托单位: Iwate Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590802/
• 关键词: asthma; allergic airway inflammation; remodeling; fibroblast; GFP; Bone marrow derived cells; collagen; mouse; 骨髄キメラマウス; G-CSF; コラーゲン沈着; 線維化; 気管支喘息; 気道リモデリング; 粘膜線維化; 骨髄細胞

Analysis of the asthma model with bone marrow transferred chimeric miceMethod : We made the murine asthma model with bone marrow transferred chimeric C57BL/6 mice. At two weeks after sensitization with Ovalbumin (OVA), the mice were exposed to OVA every other day during one month. Twenty four hours later from final exposure with OVA, we collected blood and broncho-alveolar lavage fluid (BAL) and obtained the lung tissue from these mice on 7^<th> day, 14^<th> day and 28^<th> day. In addition, we divided these mice into two groups. One group of the mice was administered intraperitoneally with G-CSF and the other group with saline as the control.Estimation of histological changes was performed. The pulmonary tissue was fixed with formaldehyde and were embedded in paraffin. On the tissue sections, we estimated infiltrated inflammatory cells into airway wall as a score semi-quantitatively with Hematoxylin-Eosin staining. We identified GFP-expressing cells in bronchial tissues under chemiluminescence microscopy and also GFP positive cells with immunohistochemistry using ant-GFP antibody.Results : On 7^<th> day after OVA exposure, eosinophils as major cells, lymphocytes and monocytes were observed in peribronchial and alveolar tissue in the chimeric mice. On 14^<th> and 28^<th> day, thickening of epithelial basement membrane and deposition of collagen in submucosal layer of bronchi became prominent. Some GFP-expressing cells were spindle-like shape under epithelium and assumed fibroblast like cells. They were also confirmed by immunohistochemistry.GFP-expressing cells increased more in the lung of the mice with G-CSF treatment than control, and collagen deposition estimated with Elastica-Masson staining decreased in G-CSF treated mice compared to control.Conclusion : Bone marrow derived cells were recruited to peribronchial tissue with allergic inflammation and might play a regulatory role in collagen deposition in the airway.

方法：用骨髓移植的嵌合体C57 BL/6小鼠建立小鼠哮喘模型。在用卵清蛋白（OVA）致敏后两周，小鼠在一个月期间每隔一天暴露于OVA。在最后一次暴露于OVA后24小时，我们收集血液和支气管肺泡灌洗液（BAL），并在第7天、第14天和第28天从这些小鼠获得肺组织<th><th><th>。此外，我们将这些小鼠分为两组。一组小鼠腹腔注射G-CSF，另一组小鼠腹腔注射生理盐水作为对照，观察组织学变化。将肺组织用甲醛固定并包埋在石蜡中。在组织切片上，我们用苏木精-伊红染色半定量地评估浸润到气道壁中的炎性细胞。结果：<th>OVA暴露后第7天，嵌合小鼠支气管周围和肺泡组织中以嗜酸性粒细胞为主，同时可见淋巴细胞和单核细胞。第14<th>、28天<th>支气管上皮基底膜增厚，粘膜下层胶原沉积明显。部分GFP表达细胞在上皮下呈梭形，呈成纤维细胞样。免疫组化结果也证实了这一点。G-CSF治疗组小鼠肺组织中GFP表达细胞比对照组增加，Elastica-Masson染色显示G-CSF治疗组小鼠肺组织中胶原沉积比对照组减少。结论：骨髓来源的细胞被募集到过敏性炎症的支气管周围组织中，并可能在气道胶原沉积中起调节作用。

项目成果

Klinefelter’s syndrome associated with systemic lupus erythematosus and autoimmune hepatitis

• DOI: 10.3109/s10165-006-0511-5
• 发表时间: 2006-10
• 期刊: Modern Rheumatology
• 影响因子: 2.2
• 作者: N. Sasaki;K. Yamauchi;R. Sato;T. Masuda;T. Sawai;H. Inoue

Anti-inflammatory actions of pranlukast, and its efficacy on asthma QOL.

普鲁司特的抗炎作用及其对哮喘 QOL 的功效。

• 发表时间: 2005
• 期刊: Proceeding of the 6th Asia Pacific Congress of Allergology and Clinical Immunology : 2004,October 4-7.Tokyo
• 作者: Osamu Matsuno;Takuya Ueno;Ryuichi Takenaka;Toshiyuki Okubo;et al.;Yamauchi K et al.
• 通讯作者: Yamauchi K et al.

Efficacy and safety of intravenous theophylline administration

静脉注射茶碱的疗效和安全性

• 发表时间: 2005
• 期刊: Respirology 10
• 作者: Zaki MH;Akuta T;Akaike T;Yamauchi K et al.
• 通讯作者: Yamauchi K et al.

Increased levels of CTGF mRNA expression in a murine model

小鼠模型中 CTGF mRNA 表达水平升高

• 发表时间: 2005
• 期刊: Allergology International 54
• 作者: Usami N;Fukui T;Kondo M;Taniguchi T;Yokoyama T;Mori S;Yokoi K;Horio Y;Shimokata K;Sekido Y;Hida T;Piao-H-M et al.
• 通讯作者: Piao-H-M et al.

Recent advances in molecular pharmacology of the histamine systems : OCT as a histamine transporter and histamine metabolism.

组胺系统分子药理学的最新进展：OCT 作为组胺转运蛋白和组胺代谢。

• 发表时间: 2006
• 期刊: J Pharmacol Sci 101
• 作者: Horikawa T;Komohara Y;Kiyota E;Terasaki Y;Takagi K;Takeya M;Ogasawara M et al.
• 通讯作者: Ogasawara M et al.