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结核性豚鼠肺肉芽肿细胞因子环境的显微解剖

Microdissection of the cytokine milieu of pulmonary granulomas from tuberculous guinea pigs.

作者信息

Ly Lan H, Russell Murat I, McMurray David N

机构信息

Department of Microbial and Molecular Pathogenesis, Texas A&M University System Health Science Center, College Station, TX 77843, USA.

出版信息

Cell Microbiol. 2007 May;9(5):1127-36. doi: 10.1111/j.1462-5822.2006.00854.x. Epub 2007 Jan 9.

DOI:10.1111/j.1462-5822.2006.00854.x
PMID:17217432
Abstract

Levels of IL-12p40, TNFalpha, TGFbeta, IFNgamma and IL-10 mRNA were assessed by laser capture microdissection followed by quantitative real-time PCR in the pulmonary granulomas of unimmunized and BCG-vaccinated guinea pigs infected by aerosol with virulent Mycobacterium tuberculosis. Lesions microdissected from unimmunized guinea pigs were overwhelmed by the pro-inflammatory TNFalpha mRNA at both 3 and 6 weeks post infection, indicating the struggle to control the mounting infection. The cytokine profile of granulomas from vaccinated guinea pigs shifted from type 1 cytokine mRNA (IFNgamma and IL-12p40) at 3 weeks to a predominantly anti-inflammatory environment (TGFbeta mRNA) at 6 weeks. The relative proportions of cytokine mRNA transcripts in the periphery of the granuloma were different from the centre, reflecting differences in cell composition and architecture. Moreover, analysis of the individual lung lobes at 6 weeks post infection suggests that heterogeneity exists in the cytokine profile between the lobes of the lung.

摘要

通过激光捕获显微切割,随后在未免疫和卡介苗接种的豚鼠经气溶胶感染强毒结核分枝杆菌后的肺肉芽肿中进行定量实时PCR,评估白细胞介素-12p40(IL-12p40)、肿瘤坏死因子α(TNFα)、转化生长因子β(TGFβ)、干扰素γ(IFNγ)和白细胞介素-10(IL-10)mRNA的水平。在感染后3周和6周,从未免疫豚鼠中显微切割的病变被促炎的TNFα mRNA所主导,这表明机体在努力控制不断增加的感染。接种疫苗的豚鼠肉芽肿的细胞因子谱从3周时的1型细胞因子mRNA(IFNγ和IL-12p40)转变为6周时主要为抗炎环境(TGFβ mRNA)。肉芽肿周边细胞因子mRNA转录本的相对比例与中心不同,反映了细胞组成和结构的差异。此外,对感染后6周的各个肺叶进行分析表明,肺叶之间的细胞因子谱存在异质性。

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