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

基本信息

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

项目摘要

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.

骨髓移植嵌合小鼠哮喘模型分析方法：采用骨髓移植嵌合C57BL/6小鼠制作小鼠哮喘模型。在卵清蛋白 (OVA) 致敏后两周，小鼠在一个月内每隔一天接触 OVA。最终接触 OVA 24 小时后，我们收集了血液和支气管肺泡灌洗液 (BAL)，并在第 7 天、第 14 天和第 28 天从这些小鼠中获取了肺组织天。此外，我们将这些小鼠分为两组。一组小鼠腹腔注射G-CSF，另一组腹腔注射生理盐水作为对照。进行组织学变化的评估。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-伊红染色半定量地估计浸润到气道壁的炎症细胞作为评分。我们在化学发光显微镜下鉴定了支气管组织中表达 GFP 的细胞，并使用 ant-GFP 抗体通过免疫组织化学鉴定了 GFP 阳性细胞。结果：OVA 暴露后第 7 天，在支气管周围观察到以嗜酸性粒细胞为主要细胞、淋巴细胞和单核细胞。和嵌合小鼠的肺泡组织。第14天和第28天，支气管粘膜下层上皮基底膜增厚和胶原沉积变得明显。一些表达 GFP 的细胞在上皮下呈纺锤状，并呈现成纤维细胞样细胞。免疫组织化学也证实了这一点。与对照组相比，接受 G-CSF 治疗的小鼠肺部中表达 GFP 的细胞比对照组增加更多，并且与对照组相比，G-CSF 治疗的小鼠中用 Elastica-Masson 染色估计的胶原蛋白沉积减少。结论：骨骨髓来源的细胞被招募到患有过敏性炎症的支气管周围组织，并且可能在气道中的胶原沉积中发挥调节作用。

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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。

DOI：
发表时间：
2005
期刊：
Proceeding of the 6th Asia Pacific Congress of Allergology and Clinical Immunology : 2004,October 4-7.Tokyo
影响因子：
0
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

DOI：
发表时间：
2005
期刊：
Respirology 10
影响因子：
0
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

DOI：
发表时间：
2005
期刊：
Allergology International 54
影响因子：
0
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。

DOI：
发表时间：
2006
期刊：
J Pharmacol Sci 101
影响因子：
0
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.

Recent advances in molecular pharmacology of the histamine systems

组胺系统分子药理学的最新进展