Microenvironments in tuberculous granulomas are delineated by distinct populations of macrophage subsets and expression of nitric oxide synthase and arginase isoforms.
Microenvironments in tuberculous granulomas are delineated by distinct populations of macrophage subsets and expression of nitric oxide synthase and arginase isoforms.
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DOI：
10.4049/jimmunol.1300113
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发表时间：
2013-07-15
期刊：
影响因子：
--
通讯作者：
Flynn JL
中科院分区：
文献类型：
--
作者：
Mattila JT;Ojo OO;Kepka-Lenhart D;Marino S;Kim JH;Eum SY;Via LE;Barry CE 3rd;Klein E;Kirschner DE;Morris SM Jr;Lin PL;Flynn JL
肉芽肿中的巨噬细胞既是结核分枝杆菌(M.tb)的抗分枝杆菌效应者，也是宿主细胞，但对肉芽肿复杂结构中巨噬细胞多样性和功能的基本方面仍知之甚少。为了解决这个问题，我们研究了猕猴和人类肉芽肿中髓系细胞的表型和与宿主防御相关的酶的表达。猕猴肉芽肿与非肉芽肿组织相比，诱导型和内皮型一氧化氮合酶(iNOS和eNOS)和精氨酸酶(Arg1和Arg2)的表达和酶活性均上调。免疫组织化学分析显示，邻近正常组织的巨噬细胞更有可能表达CD163，而细菌居住的区域的上皮样巨噬细胞则强烈表达CD11c、CD68和HAM56。钙化保护素阳性的中性粒细胞在靠近干酪的区域大量存在。INOS、eNOS、Arg1和Arg2蛋白在巨噬细胞中表达，在不同物种的肉芽肿中定位相似，上皮样巨噬细胞中eNOS的表达和iNOS/Arg1的比例高于淋巴细胞袖带中的细胞。中性粒细胞表达iNOS、Arg1和Arg2。表型和功能标记物的结合支持具有抗炎表型的巨噬细胞定位于肉芽肿的外部区域，而内部区域更有可能包含具有促炎或杀菌表型的巨噬细胞。总之，这些数据支持肉芽肿组织了微环境的概念，该微环境平衡了抗微生物抗炎反应，以限制肺部的病理。
Macrophages in granulomas are both anti-mycobacterial effector and host cell for Mycobacterium tuberculosis(M.tb), yet basic aspects of macrophage diversity and function within the complex structures of granulomas remain poorly understood. To address this, we examined myeloid cell phenotypes and expression of enzymes correlated with host defense in macaque and human granulomas. Macaque granulomas had upregulated inducible and endothelial nitric oxide synthase (iNOS and eNOS) and arginase (Arg1 and Arg2) expression and enzyme activity compared to non-granulomatous tissue. Immunohistochemical analysis indicated macrophages adjacent to uninvolved normal tissue were more likely to express CD163, while epithelioid macrophages in regions where bacteria reside strongly expressed CD11c, CD68 and HAM56. Calprotectin-positive neutrophils were abundant in regions adjacent to caseum. iNOS, eNOS, Arg1 and Arg2 proteins were identified in macrophages and localized similarly in granulomas across species, with greater eNOS expression and ratio of iNOS:Arg1 expression in epithelioid macrophages, as compared to cells in the lymphocyte cuff. iNOS, Arg1 and Arg2 expression in neutrophils was also identified. The combination of phenotypic and functional markers support that macrophages with anti-inflammatory phenotypes localized to outer regions of granulomas while the inner regions were more likely to contain macrophages with pro-inflammatory, presumably bactericidal, phenotypes. Together these data support the concept that granulomas have organized microenvironments that balance anti-microbial anti-inflammatory responses to limit pathology in the lungs.
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影响因子：
5.4
作者：
Hamann, Jorg;Koning, Nathalie;Kwakkenbos, Mark J.
通讯作者：
Kwakkenbos, Mark J.
影响因子：
64.8
作者：
通讯作者：
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影响因子：
5.4
作者：
Barron, Luke;Wynn, Thomas A.
通讯作者：
Wynn, Thomas A.
影响因子：
56.9
作者：
Darwin, KH;Ehrt, S;Nathan, CF
通讯作者：
Nathan, CF
DOI：
10.1016/s0962-8479(97)90004-6
发表时间：
1997-01-01
期刊：
TUBERCLE AND LUNG DISEASE
影响因子：
--
作者：
Adams, LB;Dinauer, MC;Krahenbuhl, JL
通讯作者：
Krahenbuhl, JL