Locachevic Gisele Aparecida, Pereira Priscilla Aparecida Tartari, Secatto Adriana, Fontanari Caroline, Galvão Alyne Fávero, Prado Morgana Kelly Borges, Zoccal Karina Furlani, Petta Tânia, Moraes Luiz Alberto Beraldo, Ramos Simone Gusmão, de Castro Fabíola Attie, Sorgi Carlos Artério, Faccioli Lúcia Helena
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, SP, Brazil.
Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14040-901 Ribeirão Preto, SP, Brazil.
Mediators Inflamm. 2015;2015:786319. doi: 10.1155/2015/786319. Epub 2015 Oct 11.
Erythropoietin (EPO) is a key hormone involved in red blood cell formation, but its effects on nonerythroid cells, such as macrophages, have not been described. Macrophages are key cells in controlling histoplasmosis, a fungal infection caused by Histoplasma capsulatum (Hc). Considering that little is known about EPO's role during fungal infections and its capacity to activate macrophages, in this study we investigated the impact of EPO pretreatment on the alveolar immune response during Hc infection. The consequence of EPO pretreatment on fungal infection was determined by evaluating animal survival, fungal burden, activation of bronchoalveolar macrophages, inflammatory mediator release, and lung inflammation. Pretreatment with EPO diminished mononuclear cell numbers, increased the recruitment of F4/80(+)/CD80(+) and F4/80(+)/CD86(+) cells to the bronchoalveolar space, induced higher production of IFN-γ, IL-6, MIP-1α, MCP-1, and LTB4, reduced PGE2 concentration, and did not affect fungal burden. As a consequence, we observed an increase in lung inflammation with extensive tissue damage that might account for augmented mouse mortality after infection. Our results demonstrate for the first time that EPO treatment has a deleterious impact on lung immune responses during fungal infection.
促红细胞生成素（EPO）是参与红细胞生成的关键激素，但其对非红细胞系细胞（如巨噬细胞）的作用尚未见报道。巨噬细胞是控制组织胞浆菌病（一种由荚膜组织胞浆菌（Hc）引起的真菌感染）的关键细胞。鉴于对EPO在真菌感染中的作用及其激活巨噬细胞的能力了解甚少，在本研究中，我们调查了EPO预处理对Hc感染期间肺泡免疫反应的影响。通过评估动物存活率、真菌负荷、支气管肺泡巨噬细胞的激活、炎症介质释放和肺部炎症来确定EPO预处理对真菌感染的影响。EPO预处理可减少单核细胞数量，增加F4/80(+)/CD80(+)和F4/80(+)/CD86(+)细胞向支气管肺泡腔的募集，诱导更高水平的IFN-γ、IL-6、MIP-1α、MCP-1和LTB4产生，降低PGE2浓度，且不影响真菌负荷。结果，我们观察到肺部炎症增加，伴有广泛的组织损伤，这可能是感染后小鼠死亡率增加的原因。我们的结果首次证明，EPO治疗对真菌感染期间的肺部免疫反应有有害影响。
