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人甘露聚糖结合凝集素相关丝氨酸蛋白酶 2 对卡介苗感染诱导的 BALB/c 小鼠肺部肉芽肿形成的影响。

Effects of hMASP-2 on the formation of BCG infection-induced granuloma in the lungs of BALB/c mice.

机构信息

Department of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.

The First Hospital of Lanzhou University, Lanzhou, 730000, China.

出版信息

Sci Rep. 2017 May 23;7(1):2300. doi: 10.1038/s41598-017-02374-z.

Abstract

Tuberculosis, caused by Mycobacterium tuberculosis, affects the functions of the lung and causes high morbidity and mortality rates worldwide. MASP-2 is an executioner enzyme, which plays an essential role in the activation of lectin pathway. In our previous studies, the MASP-2 played a dual role in promoting the progress of lesions in BCG-infected rabbit skin models. However, the really effects of MASP-2 on tuberculosis are unknown. The aim of this study was to investigate the effects of MASP-2 in granuloma formation with BCG-infected mice. Compared to the control group, rAd-hMASP-2 treated group showed increasing in survival rate of BCG-infected mice (P = 0.042), and decreasing of bacteria loads (P = 0.005) in the lung tissue. MASP-2 displayed a protective efficacy in BCG-infected mice, which promoted the activation and recruitment of macrophages and lymphocytes to the granuloma. Moreover, the data obtained from the ELISA and RT-PCR demonstrated that mRNA expression for IL-6, CCL12, CCL2 and cytokines of IFN-γ, TNF-α in lung were significantly elevated by treatment of rAd-hMASP-2. Those findings provided an evidence that MASP-2 may be as a newly immunomodulatory in targeting granuloma formation, which displayed a potential protective role in control of tuberculosis.

摘要

结核病是由结核分枝杆菌引起的,它会影响肺部功能,导致全球发病率和死亡率居高不下。甘露聚糖结合凝集素相关丝氨酸蛋白酶 2(MASP-2)是一种执行酶,在凝集素途径的激活中发挥着重要作用。在我们之前的研究中,MASP-2 在促进卡介苗(BCG)感染兔皮肤模型病变进展中起双重作用。然而,MASP-2 对结核病的真正作用尚不清楚。本研究旨在探讨 MASP-2 在 BCG 感染小鼠肉芽肿形成中的作用。与对照组相比,rAd-hMASP-2 处理组的 BCG 感染小鼠存活率升高(P=0.042),肺组织中的细菌载量降低(P=0.005)。MASP-2 在 BCG 感染小鼠中表现出保护作用,促进了巨噬细胞和淋巴细胞向肉芽肿的激活和募集。此外,ELISA 和 RT-PCR 获得的数据表明,rAd-hMASP-2 处理显著上调了肺中 IL-6、CCL12、CCL2 和 IFN-γ、TNF-α 等细胞因子的 mRNA 表达。这些发现为 MASP-2 可能作为一种新的免疫调节因子靶向肉芽肿形成提供了证据,显示其在控制结核病方面具有潜在的保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0da/5442121/c66f4120cbeb/41598_2017_2374_Fig1_HTML.jpg

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