Amphotericin B formulations variably enhance antifungal activity of human neutrophils and monocytes against Fusarium solani:: comparison with Aspergillus fumigatus
Amphotericin B formulations variably enhance antifungal activity of human neutrophils and monocytes against Fusarium solani:: comparison with Aspergillus fumigatus
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DOI：
10.1093/jac/dkn036
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发表时间：
2008-04-01
影响因子：
5.2
通讯作者：
Roilides, Emmanuel
中科院分区：
文献类型：
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作者：
Dotis, John;Simitsopoulou, Maria;Roilides, Emmanuel
目的：两性霉素 B (AMBF) 脂质制剂广泛用于治疗由烟曲霉和茄病镰刀菌引起的危及生命的感染。我们的目的是比较四种 AMBF、脱氧胆酸盐 (DAMB)、脂质体 (LAMB)、脂质复合物 (ABLC) 和胶体分散体 (ABCD) 对人中性粒细胞 (PMN) 和单核细胞 (MNC) 对烟曲霉和茄病菌菌丝的氧化抗真菌活性的免疫调节作用。方法：将人 PMN 和 MNC 用 1 或 1 种预孵育。 5 mg/L DAMB，LAMB、ABLC 和 ABCD 各为 5 或 25 mg/L。然后通过 XTT 测定评估菌丝损伤，并通过细胞色素 c 测定评估 O-2(-) 产生。结果：所有药剂均导致吞噬细胞对烟曲霉和茄病镰刀菌诱导的菌丝损伤增加（P < 0.05）。与低浓度相比，高浓度的 AMBF 对两种真菌引起更高的吞噬细胞诱导的菌丝损伤。然而，在菌丝损伤增强程度方面，AMBF 或实质性效应细胞：靶标比率依赖性差异均不具有一致的优越性。相比之下，PMN 或 MNC 在菌丝攻击后产生的 O-2(-) 一般不受任何 AMBF 的影响。 F. solani菌丝对H2O2的抵抗力显着高于A. fumigatus。结论：这些结果表明AMBF对吞噬细胞诱导的A. fumigatus和F. solani菌丝损伤有不同程度的增强作用。其他杀菌机制（可能是非氧化性的）更有可能介导 AMBF 对宿主防御这两种医学上重要的丝状真菌的免疫调节作用。
Objectives: Lipid formulations of amphotericin B (AMBF) are widely used in the treatment of life-threatening infections caused by Aspergillus fumigatus and Fusarium solani. We aimed to compare the immunomodulatory effects of four AMBF, deoxycholate (DAMB), liposomal (LAMB), lipid complex (ABLC) and colloidal dispersion (ABCD), on the oxidative antifungal activities of human neutrophils (PMNs) and monocytes (MNCs) against hyphae of A. fumigatus and F. solani.Methods: Human PMNs and MNCs were pre-incubated with 1 or 5 mg/L DAMB and 5 or 25 mg/L for each of LAMB, ABLC and ABCD. Hyphal damage was then assessed by XTT assay, and O-2(-) production was assessed by cytochrome c assay.Results: All agents resulted in increased hyphal damage induced by phagocytes against both A. fumigatus and F. solani (P < 0.05). The high concentrations of AMBF elicited higher phagocyte-induced hyphal damage of both fungi than the low concentrations. There was, however, no consistent superiority of any of the AMBF or substantial effector cell:target ratio-dependent differences in the degree of hyphal damage enhancement. By comparison, O-2(-) produced by PMNs or MNCs upon hyphal challenge was not generally affected by any of the AMBF. F. solani hyphae were significantly more resistant to H2O2 than A. fumigatus.Conclusions: These findings suggest that AMBF have enhancing effects of variable degree on phagocyte-induced hyphal damage of A. fumigatus and F. solani. Other fungicidal mechanisms, perhaps non-oxidative, are more likely to mediate these immunomodulatory effects of AMBF on host defence against the two medically important filamentous fungi.