来自健康小鼠或卵白蛋白诱导的肺部炎症小鼠的骨髓单核细胞对过敏性哮喘小鼠的作用
2014/11/05
摘要
前言:哮喘是一种慢性的炎症反应,它可导致骨髓细胞组成的某些变化。我们假设来自卵白蛋白(OVA)诱导的肺部炎症小鼠以及来自健康小鼠的骨髓单核细胞(BMMCs)对过敏性哮喘小鼠模型具有不同作用。
方法:C57BL/6小鼠被随机分为两组。OVA组小鼠用卵白蛋白使其致敏和激发,健康小鼠(对照组)则使用相同的方法给予生理盐水。骨髓单核细胞在最后一次致敏24h后用流式细胞仪进行分析。细胞分析后另一组OVA小鼠被随机分为3个亚组,一组气管内给予生理盐水(BMMC-SAL),一组给予健康小鼠的骨髓单核细胞(BMMC-Control),另一组给予OVA组小鼠的骨髓单核细胞(BMMC-OVA),每只小鼠给予2x106个细胞,均在末次激发后24小时。
结果:与BMMC-Control组相比,BMMC-OVA组小鼠的嗜酸性粒细胞、单核细胞以及造血前体细胞的比例升高,但其间充质干细胞的数量减少。两组小鼠的骨髓单核细胞均可降低受体小鼠的气道阻力、肺泡的塌陷、气道狭窄指数、嗜酸性粒细胞浸润、肺泡隔内的胶原纤维含量、以及肺匀浆内的细胞因子(IL)-4、IL-5、IL-13、干扰素-γ、转移生长因子-β和血管内皮生长因子的含量。但是,BMMC-Control组小鼠的骨髓单核细胞的疗效更明显。
结论:BMMC-Control组与BMMC-OVA组单核细胞均减弱了气道的炎症及重塑。但是,可能由于两组小鼠的骨髓单核细胞的组成和/或性能不同,BMMC-Control组的骨髓单核细胞可更好地改善受体小鼠的肺形态功能。
(杨冬 审校)
Stem Cell Res Ther. 2014 Sep 9;5(5):108. [Epub ahead of print]
Effects of bone marrow mononuclear cells from healthy or ovalbumin-induced lung inflammation donors on recipient allergic asthma mice.
Abreu SC, Antunes MA, Mendonça L, Branco VC, de Melo EB, Olsen PC, Diaz BL, Weiss DJ, Paredes BD, Xisto DG, Morales MM, Rocco PR.
ABSTRACT
INTRODUCTION: Asthma is characterized by a chronic inflammatory process which may lead to several changes in bone marrow cell composition. We hypothesized that bone marrow mononuclear cells (BMMCs) obtained from ovalbumin (OVA)-induced lung inflammation mice may promote different effects compared to BMMCs from healthy donors in a model of allergic asthma.
METHODS: C57BL/6 mice were randomly assigned to two groups. In the OVA group, mice were sensitized and challenged with ovalbumin, while healthy animals (control group) received saline using the same protocol. BMMCs were analyzed by flow cytometry 24 hours after the last challenge. After BMMC characterization, another group of OVA mice were further randomized into three subgroups to receive intratracheal saline (BMMC-SAL), BMMCs from control or BMMCs from OVA mice (BMMC-Control and BMMC-OVA, respectively; 2x106 cells/mouse), 24 hours after the last challenge.
RESULTS: BMMC-OVA exhibited an increased percentage of eosinophils, monocytes and hematopoietic precursors, while mesenchymal stem cells decreased, as compared with BMMC-Control. BMMCs from both donor groups reduced airway resistance, alveolar collapse, bronchoconstriction index, eosinophil infiltration, collagen fiber content in alveolar septa and levels of interleukin (IL)-4, IL-5, IL-13, interferon-gamma, transforming growth factor-beta, and vascular endothelial growth factor in lung homogenates. However, the benefits of BMMCs were significantly more pronounced when cells were obtained from control donors.
CONCLUSION: Both BMMC-Control and BMMC-OVA reduced the inflammatory and remodeling processes; nevertheless, BMMC-Control led to a greater improvement in lung morphofunction, which may be due to different BMMC composition and/or properties.
Stem Cell Res Ther. 2014 Sep 9;5(5):108. [Epub ahead of print]
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哮喘与多种固有的抗病毒信号通路的改变相关
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