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Identification of Constituents of Human Neutrophil Azurophil Granules That Mediate Fungistasis againstHistoplasma capsulatum

机译:人嗜中性粒细胞Azurophil颗粒的成分组成,介导针对荚膜丝虫的真菌病

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Previously we demonstrated that human neutrophils mediate potent and long-lasting fungistasis against Histoplasma capsulatumyeasts and that all of the fungistatic activity resides in the azurophil granules. In the present study, specific azurophil granule constituents with fungistatic activity were identified by incubation with H. capsulatum yeasts for 24 h and by quantifying the subsequent growth of yeasts via the incorporation of [3H]leucine. Human neutrophil defensins HNP-1, HNP-2, and HNP-3 inhibited the growth of H. capsulatum yeasts in a concentration-dependent manner with maximum inhibition at 8 μg/ml. At a concentration of 4 μg/ml, all possible paired combinations of defensins exhibited additive fungistatic activity against H. capsulatum yeasts. Cathepsin G and bactericidal-permeability-increasing protein (BPI) also mediated fungistasis against H. capsulatum in a concentration-dependent manner. The fungistatic activities of combinations of cathepsin G and BPI were additive, as were those of combinations of cathepsin G or BPI with HNP-1, HNP-2, and HNP-3. Lysozyme and elastase exhibited modest antifungal activity, and azurocidin and proteinase 3 exhibited no significant fungistasis against H. capsulatum yeasts. Thus, defensins, cathepsin G, and BPI are the major anti-H. capsulatum effector molecules in the azurophil granules of human neutrophils.
机译:先前,我们证明了人类嗜中性粒细胞介导了针对荚膜组织胞浆酵母的有效且持久的真菌作用,并且所有的抑菌活性都位于嗜蓝粒颗粒中。在本研究中,通过与 H孵育鉴定了具有抑菌活性的特定的类固氮蓝颗粒成分。并通过[[sup> 3 H]亮氨酸的掺入来定量随后酵母的生长。人中性粒细胞防御素HNP-1,HNP-2和HNP-3抑制了 H的生长。荚膜酵母具有浓度依赖性,最大抑制量为8μg/ ml。在浓度为4μg/ ml时,防御素的所有可能的配对组合均表现出针对 H的累加真菌活性。荚膜酵母。组织蛋白酶G和杀菌通透性增强蛋白(BPI)也介导了针对 H的真菌病。荚膜浓度依赖性。组织蛋白酶G和BPI的组合的抑菌活性是累加的,组织蛋白酶G或BPI与HNP-1,HNP-2和HNP-3的组合的抑菌活性也是相加的。溶菌酶和弹性蛋白酶表现出适度的抗真菌活性,而天青霉素和蛋白酶3没有表现出针对 H的显着真菌作用。荚膜酵母。因此,防御素,组织蛋白酶G和BPI是主要的抗-H抗体。人嗜中性粒细胞的嗜蓝粒颗粒中的荚膜效应分子。

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