Inhibition of nitric oxide production by macrophages in chromoblastomycosis:: a role for Fonsecaea pedrosoi melanin
Inhibition of nitric oxide production by macrophages in chromoblastomycosis:: a role for Fonsecaea pedrosoi melanin
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DOI：
10.1007/s11046-005-0228-6
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发表时间：
2006-04-01
期刊：
影响因子：
5.5
通讯作者：
Tosta, CE
中科院分区：
文献类型：
--
作者：
Bocca, AL;Brito, PMS;Tosta, CE
着色芽生菌病是一种慢性和进行性深部真菌病，通常发现于热带和亚热带地区。Fonsecaea pedroplasty被认为是其最常见的病原体，并引起典型的肉芽肿性炎症反应，其程度反映了宿主的免疫状态。由于巨噬细胞在感染的控制中发挥着重要作用，本研究旨在调查生产的氧反应性标本，吞噬能力和生产的一氧化氮（NO）的巨噬细胞采用体外试验和体内模型的着色芽生菌病。我们的结果表明，在感染过程中，腹腔巨噬细胞的吞噬能力和H2O2的产生增加，但也减少了产生NO的能力。pedrophilin刺激H2O2的生产在体外，但没有合成NO。IFN γ和LPS刺激的巨噬细胞与黑色素，从真菌中获得的孵育，抑制NO的产生。在接种后第30天或第60天，对感染动物的肝脏和脾脏进行检查，结果显示肉芽肿的数量和大小逐渐增加，表明巨噬细胞被适当动员和激活。我们的数据表明，宿主不能清除F。导致慢性疾病的小儿麻痹症至少部分是由于真菌产生的黑色素抑制巨噬细胞的NO合成。
Chromoblastomycosis is a chronic and progressive deep mycosis that is usually found in tropical and subtropical areas. Fonsecaea pedrosoi is considered its most frequent etiologic agent and causes a typical granulomatous inflammatory response, whose degree reflects the immune status of the host. Since macrophages play a fundamental role in the control of the infection, this study aimed at investigating the production of oxygen reactive specimens, the phagocytic capacity and the production of nitric oxide (NO) by macrophages employing in vitro assays and an in vivo model of chromoblastomycosis. Our results demonstrated that, during the infection, peritoneal macrophages show an increased phagocytic capacity and H2O2 production, but also a reduced ability to produce NO. Moreover, F. pedrosoi stimulated H2O2 production in vitro but not the synthesis of NO. The incubation of IFN gamma and LPS-stimulated macrophages with melanin, obtained from the fungus, inhibited NO production. Examination of the liver and spleen of infected animals, at day 30 or 60 following inoculation, showed a progressive increase in the number and size of granulomas, indicating that macrophages are properly mobilized and activated. Our data suggest that the inability of the host to clear F. pedrosoi, leading to a chronic disease, is due, at least in part, to the inhibition of NO synthesis by macrophages by fungus-produced melanin.