Blasi E, Barluzzi R, Mazzolla R, Tancini B, Saleppico S, Puliti M, Pitzurra L, Bistoni F
Department of Biomedical Sciences, University of Modena, Italy.
J Neuroimmunol. 1995 Apr;58(1):111-6. doi: 10.1016/0165-5728(95)00016-u.
In the present paper, we investigated the involvement of cryptococcal melanogenesis and macrophage nitric oxide (NO) production in the accomplishment of anticryptococcal activity by microglial effector cells, using the murine cell line BV-2. We demonstrate that the constitutive levels of anticryptococcal activity exerted by BV-2 cells is significantly enhanced upon interferon gamma plus lipopolysaccharide treatment. The phenomenon, which occurs with no enhancement of phagocytic activity, is associated with the production of high levels of NO and is abolished by addition of NG-monomethyl-L-arginine. Comparable patterns of results are observed employing either unopsonized or opsonized microbial targets, the latter microorganisms being markedly more susceptible to BV-2 cell antimicrobial activity. Furthermore, melanization of Cryptococcus neoformans significantly reduces its susceptibility to BV-2 antimicrobial activity, regardless of the fact that activated macrophages or opsonized microorganisms have been employed. In conclusion, our results provide evidence that NO-dependent events are involved in the fulfillment of anticryptococcal activity by activated microglial cells and that fungal melanization is a precious escamotage through which C. neoformans overcomes host defenses.
在本论文中，我们使用小鼠细胞系BV-2，研究了隐球菌黑色素生成和巨噬细胞一氧化氮（NO）产生在小胶质效应细胞实现抗隐球菌活性过程中的作用。我们证明，经干扰素γ加脂多糖处理后，BV-2细胞发挥的抗隐球菌活性的基础水平显著增强。这种现象在吞噬活性未增强的情况下发生，与高水平NO的产生相关，并且添加NG-单甲基-L-精氨酸后该现象消失。使用未调理或调理过的微生物靶标均观察到类似的结果模式，后者微生物对BV-2细胞抗菌活性明显更敏感。此外，新型隐球菌的黑色素化显著降低了其对BV-2抗菌活性的敏感性，无论是否使用了活化的巨噬细胞或调理过的微生物。总之，我们的结果提供了证据，表明依赖NO的事件参与了活化的小胶质细胞实现抗隐球菌活性的过程，并且真菌黑色素化是新型隐球菌克服宿主防御的一种重要手段。
