Nishikaku Angela Satie, Molina Raphael Fagnani Sanchez, Ribeiro Luciana Cristina, Scavone Renata, Albe Bernardo Paulo, Cunha Cláudia Silva, Burger Eva
Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Avenida Professor Lineu Prestes, 1730, Cidade Universitária, São Paulo 05508-900, Brazil.
Med Microbiol Immunol. 2009 May;198(2):123-35. doi: 10.1007/s00430-009-0113-x. Epub 2009 Apr 10.
The role of nitric oxide (NO) in granulomas of Paracoccidioides brasiliensis-infected inducible NO synthase-deficient C57BL/6 mice (iNOS KO) and their wild-type counterparts and its association with osteopontin (OPN) and matrix metalloproteinases (MMPs) was studied. At 15 days after infection (DAI), iNOS KO mice showed compact and necrotic granulomas with OPN+ macrophages and multinucleated giant cells, whereas wild-type mice developed loose granulomas with many fungi and OPN+ cells distributed throughout the tissue. In addition, high OPN levels and fungal load were observed in iNOS KO mice. Both experimental groups had MMP-9 activity. At 120 DAI, iNOS KO had smaller granulomas with OPN+ cells, lower OPN levels, lower fungal load and decreased MMP-9 activity compared with wild-type mice. These findings suggest that NO has an important role in granuloma modulation, by controlling OPN and MMP production, as well as by inducing loose granulomas formation and fungal dissemination, resulting, at later phases, in progression of paracoccidioidomycosis.
研究了一氧化氮（NO）在巴西副球孢子菌感染的诱导型一氧化氮合酶缺陷型C57BL/6小鼠（iNOS基因敲除小鼠）及其野生型对照小鼠肉芽肿中的作用，以及它与骨桥蛋白（OPN）和基质金属蛋白酶（MMPs）的关系。感染后15天（DAI），iNOS基因敲除小鼠表现出致密且坏死的肉芽肿，伴有OPN+巨噬细胞和多核巨细胞，而野生型小鼠形成疏松的肉芽肿，组织内有许多真菌和OPN+细胞分布。此外，在iNOS基因敲除小鼠中观察到较高的OPN水平和真菌载量。两个实验组均有MMP-9活性。与野生型小鼠相比，在感染后120天，iNOS基因敲除小鼠的肉芽肿较小，OPN+细胞较少，OPN水平较低，真菌载量较低，MMP-9活性降低。这些发现表明，NO在肉芽肿调节中具有重要作用，它通过控制OPN和MMP的产生，以及诱导疏松肉芽肿的形成和真菌播散，导致在疾病后期副球孢子菌病的进展。
