Polarization of T-helper 2 to 1 phenotype has arisen in rat asthmatic pulmonary tissue after intra-tracheal administration of bone marrow-derived c-Kit+ cells

Fatemeh Mir-ershadi, M. Ahmadi, R. Rahbarghazi, Hossein Heiran, A. Delkhosh, Majid Khaksar, R. Keyhanmanesh
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Abstract

Introduction: This study investigated the paracrine therapeutic effects of intra-tracheal administration of bone marrow-derived c-Kit+and c-Kit- cells on the T helper (Th)1/Th2 balance in ovalbumin-induced acute asthma in male rats. Methods: Forty male Wistar rats were randomly allocated into four experimental groups; healthy (group C) and sensitized (group S) rats received PBS (Phosphate-buffered saline); sensitized rats received PBS containing c-Kit- (group S+c-Kit- ) and c-Kit+cells (group S+c-Kit+). Total and percentages of differential leukocytes were calculated in bronchoalveolar Lavage. The lung cellular contents of interleukin (IL)-4, IL-10, and interferon gamma (IFN-γ) mRNAs were measured quantitatively. Moreover, the existence of excessive collagen deposition in pulmonary interstitial space was evaluated through Masson’s trichrome staining. Results: The results showed the successful homing of c-Kit+cells into the asthmatic niche. The significantly increased total number of leukocyte, eosinophil, neutrophil, and IL-4 mRNA levels, as well as decreased lymphocyte count, IL-10, IFN-γ mRNAs, and IL-4/IFN-γ ratio, were observed in asthmatic rats compared to C group (P<0.001). C-Kit+cells, but not c-Kit- cells, had the potential to participate in these changes (P<0.001 to P<0.05). The deposition of collagen fibers in the asthmatic pulmonary tissue decreased after administration of both c-Kit+and c-Kit-cells, which were more prominent in the S+c-Kit+group. Conclusions: The results of the current experiment highlighted the therapeutic capacity of c-Kit+cells in the alleviation of asthmatic changes at the cellular level.
气管内注射源自骨髓的 c-Kit+ 细胞后,大鼠哮喘肺组织中的 T 辅助细胞 2 表型极化为 1 表型
简介本研究探讨了气管内注射骨髓来源的 c-Kit+ 和 c-Kit- 细胞对卵清蛋白诱导的雄性大鼠急性哮喘中 T 辅助细胞(Th)1/Th2 平衡的辅助治疗作用。研究方法将 40 只雄性 Wistar 大鼠随机分为 4 个实验组:健康大鼠(C 组)和致敏大鼠(S 组)接受磷酸盐缓冲盐水(PBS);致敏大鼠接受含有 c-Kit- 细胞(S+c-Kit- 组)和 c-Kit+ 细胞(S+c-Kit+ 组)的 PBS。计算支气管肺泡灌洗液中差异白细胞的总数和百分比。白细胞介素(IL)-4、IL-10 和γ干扰素(IFN-γ)mRNA 的含量进行了定量测定。此外,还通过马森三色染色法评估了肺间质中是否存在过度胶原沉积。结果显示结果显示,c-Kit+细胞成功进入哮喘龛位。与 C 组相比,哮喘大鼠的白细胞总数、嗜酸性粒细胞、中性粒细胞和 IL-4 mRNA 水平明显增加,淋巴细胞数量、IL-10、IFN-γ mRNA 和 IL-4/IFN-γ 比值下降(P<0.001)。C-Kit+ 细胞,而非 c-Kit- 细胞,有可能参与这些变化(P<0.001 至 P<0.05)。使用 c-Kit+ 和 c-Kit 细胞后,哮喘肺组织中胶原纤维的沉积均有所减少,其中 S+c-Kit+ 组的变化更为明显。结论本次实验的结果凸显了 c-Kit+ 细胞在细胞水平上缓解哮喘变化的治疗能力。
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