骨髓源性成体干细胞在过敏性哮喘转基因小鼠模型中的作用。

The role of bone marrow-derived adult stem cells in a transgenic mouse model of allergic asthma.

机构信息

Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

出版信息

Respiration. 2012;83(1):74-80. doi: 10.1159/000330013. Epub 2011 Sep 30.

DOI:10.1159/000330013

PMID:21968331

Abstract

BACKGROUND

Asthmatic airway remodeling is an abnormal injury/repair process of the small airways caused by chronic inflammation in which the quantities of multiple cells increase dramatically. However, the origin of these proliferative cells is still undetermined.

OBJECTIVE

The aim of this study was to examine whether bone marrow (BM)-derived adult stem cells are responsible for the proliferative cells in asthmatic airway remodeling.

METHODS

Adult mice were durably engrafted with BM isolated from green fluorescent protein (GFP) transgenic mice. Using GFP BM chimera mice, an ovalbumin (OVA)-induced chronic asthma mouse model was established. The distribution of BM-derived GFP+ cells in the lungs of chronic asthma mice was detected by fluorescence microscopy. The phenotype of BM-derived GFP+ cells in the lung tissues of chronic asthma mice was analyzed by flow cytometry.

RESULTS

BM chimera mice were successfully generated, with no detectable radioactive inflammation observed. Using BM chimera mice, we established a mouse model of chronic asthma characterized by a significant increase in the thickness of the airway subepithelial basement membrane and smooth muscle layers. OVA treatment caused many GFP+ cells to appear at sites of small airway inflammation. The extravascular localization of some GFP+ cells and their morphology were not consistent with leukocytes. Flow cytometric analysis of lung cells revealed a significant increase in type I collagen (Col I)+GFP+ cells and α-smooth muscle actin (α-SMA)+GFP+ cells in OVA-treated GFP BM chimera mice.

CONCLUSIONS

Considerable numbers of Col I- and α-SMA-producing cells originated from BM in the lung tissues of mice with OVA-induced chronic asthma.

摘要

背景

哮喘气道重塑是一种由慢性炎症引起的小气道异常损伤/修复过程，其中多种细胞数量显著增加。然而，这些增殖细胞的起源仍未确定。

目的

本研究旨在探讨骨髓（BM）来源的成体干细胞是否是哮喘气道重塑中增殖细胞的来源。

方法

通过将绿色荧光蛋白（GFP）转基因小鼠的 BM 持久移植到成年小鼠体内，建立 GFP BM 嵌合体小鼠。利用 GFP BM 嵌合体小鼠，建立卵清蛋白（OVA）诱导的慢性哮喘小鼠模型。荧光显微镜检测慢性哮喘小鼠肺部 BM 衍生的 GFP+细胞的分布。流式细胞术分析慢性哮喘小鼠肺部 BM 衍生的 GFP+细胞的表型。

结果

成功构建了 BM 嵌合体小鼠，未观察到放射性炎症。利用 BM 嵌合体小鼠，我们建立了一种慢性哮喘小鼠模型，其气道上皮下基底膜和平滑肌层的厚度显著增加。OVA 处理导致许多 GFP+细胞出现在小气道炎症部位。一些 GFP+细胞的血管外定位及其形态与白细胞不一致。对肺细胞的流式细胞术分析显示，OVA 处理的 GFP BM 嵌合体小鼠中Ⅰ型胶原（Col I）+GFP+细胞和α-平滑肌肌动蛋白（α-SMA）+GFP+细胞显著增加。