Miltefosine enhances phagocytosis but decreases nitric oxide production by peritoneal macrophages of C57BL/6 mice
Miltefosine enhances phagocytosis but decreases nitric oxide production by peritoneal macrophages of C57BL/6 mice
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DOI：
10.1016/j.intimp.2012.03.016
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发表时间：
2012-05-01
影响因子：
5.6
通讯作者：
Souza Kueckelhaus, Selma Aparecida
中科院分区：
文献类型：
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作者：
Ponte, Charlene Barreto;Rocha Alves, Erica Alessandra;Souza Kueckelhaus, Selma Aparecida
米替福辛是一种抗癌药物，目前用于治疗内脏和皮肤利什曼病，还具有广谱的杀真菌和抗阿米巴活性。它作用于寄生虫膜的磷脂和糖蛋白的代谢。我们的研究旨在评估米替福辛（0.4至50.0μg/mL）对C57BL/6小鼠巨噬细胞吞噬作用和一氧化氮生成的影响，以阐明该药物对偏向Th1反应的C57BL/6品系小鼠巨噬细胞的免疫调节作用。用米替福辛体外处理腹膜巨噬细胞，并评估致敏或非致敏酿酒酵母的吞噬作用。通过格里斯反应评价NO的产生。在1.6μg/mL和50.0μg/mL浓度下，米替福辛分别使未经调理的酿酒酵母的吞噬作用增加59.7%和214.3%。对于通过调理素受体的吞噬作用，米替福辛 (50.0 μg/mL) 使吞噬指数增加 208.6%（p = 0.04，配对 t 检验）。米替福辛（50.0 μg/mL）使巨噬细胞产生的 NO 减少 39.3%。然而，巨噬细胞感染亚马逊利什曼原虫后，用米替福辛 (50.0 μg/mL) 治疗可使 NO 产量增加 73.4%（p = 0.01，Wilcoxon 检验）。我们的数据显示，除了米替福辛的抗菌作用外，该药物还对 C57BL/6 小鼠的巨噬细胞显示出免疫调节作用，改善吞噬作用并减少 NO 产生，但当巨噬细胞先前感染亚马逊乳杆菌时，能够增加 NO 产生。这些结果表明，米替福辛可能通过改善巨噬细胞的先天免疫反应，有利于传染病的更好发展。 (C) 2012 Elsevier B.V. 保留所有权利。
Miltefosine is an anticancer drug currently used to treat visceral and cutaneous leishmaniasis, also presents a broad-spectrum of fungicidal and antiamoebae activities. It acts on the metabolism of phospholipids and glycoproteins of the membrane of parasites. Our study aimed to evaluate the effects of miltefosine (0.4 to 50.0 mu g/mL) on the phagocytosis and nitric oxide production by macrophages of C57BL/6 mice to clarify the immunomodulatory effects of the drug on macrophages of C57BL/6, strain mice that is biased to Th1 response. Peritoneal macrophages were in vitro treated with miltefosine and phagocytosis of sensitized or nonsensitized Saccharomyces cerevisiae was assessed. NO production was evaluated by Griess reaction. In the concentration of 1.6 mu g/mL and 50.0 mu g/mL, miltefosine increased phagocytosis of non-opsonized S. cerevisiae in 59.7% and 214.3%, respectively. For phagocytosis through opsonin receptors, miltefosine (50.0 mu g/mL) increased the phagocytic index in 208.6% ( p = 0.04, paired t test). Miltefosine (50.0 mu g/mL) decreased in 39.3% NO production by macrophages. However, treatment with miltefosine (50.0 mu g/mL) after infection of macrophages with Leishmania amazonensis increased NO production in 73.4% (p =0.01, Wilcoxon test). Our data showed that, besides the antimicrobial effect of miltefosine, the drug showed immunomodulatory effects on macrophages of C57BL/6 mice, improving phagocytosis and decreasing NO production, but was able to increase NO production when macrophages were previously infected with L amazonensis. These results suggest that miltefosine may favor the better evolution of infectious diseases by improving the innate immune response of macrophages. (C) 2012 Elsevier B.V. All rights reserved.