The interaction of human monocytes, monocyte-derived macrophages, and polymorphonuclear neutrophils with caspofungin (MK-0991), an echinocandin, for antifungal activity against Aspergillus fumigatus
The interaction of human monocytes, monocyte-derived macrophages, and polymorphonuclear neutrophils with caspofungin (MK-0991), an echinocandin, for antifungal activity against Aspergillus fumigatus
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DOI：
10.1016/s0732-8893(00)00236-4
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发表时间：
2001-02-01
影响因子：
2.9
通讯作者：
Stevens, DA
中科院分区：
文献类型：
--
作者：
Chiller, T;Farrokhshad, K;Stevens, DA
研究了人效应细胞与卡泊芬净（MK-0991）（一种1，3-β-D葡聚糖合成酶抑制剂）之间的协同作用对烟曲霉的抗真菌活性。将卡泊芬净与人单核细胞（Monos）、单核细胞衍生的巨噬细胞（MDM）或多形核中性粒细胞（PMN）共培养24小时，以对抗A.使用XTT代谢测定评估烟曲霉和抗真菌活性。0.1 μ g/ml和0.05 μ g/ml的卡泊芬净或单用Monos对幼苗产生显著抑制。显微镜下，这与生长缓慢和发育不良的畸形菌丝有关。在单核细胞培养物中加入0.1 μ g/ml和0.05 μ g/ml的卡泊芬净增加了抗真菌活性。联合用药的抑制作用显著大于单独用药（P < .01）和单独使用Monos（P < .01）。MDM对曲霉菌丝生长有抑制作用。0.1 μ g/ml和0.05 μ g/ml的卡泊芬净与巨噬细胞培养物的组合增加了抗真菌活性。联合用药的生长抑制作用显著大于单独用药（P <0.01）和单独使用MDM（P <0.01）。对中性粒细胞和卡泊芬净无显著干扰或增强。这些数据支持卡泊芬净对A.烟曲霉在体外，并表明与人效应细胞的协同活性。这表明卡泊芬净在体内会增加效力，因为它与宿主对A.烟熏。(C)2001 Elsevier Science Inc. All rights reserved.
The collaboration between human effector cells and caspofungin (MK-0991), a 1,3-beta -D,glucan synthase inhibitor, was studied for antifungal activity against Aspergillus fumigatus. Caspofungin was co-cultured for 24h with either human monocytes (Monos), monocyte-derived macrophages (MDM), or polymorphonuclear neutrophils (PMN) against germlings of A. fumigatus and antifungal activity assessed using the XTT metabolic assay. Caspofungin at 0.1 mug/ml and 0.05 mug/ml or Monos alone against germlings caused significant inhibition. Microscopically this was correlated with less growth and stunted malformed hyphae. The addition of caspofungin at 0.1 mug/ml and 0.05 mug/ml to the monocyte cultures increased antifungal activity. The inhibition of the combination was significantly greater than drug alone (P < .01) and Monos alone (P < .01). MDM against Aspergillus germlings inhibited hyphal growth. The combination of caspofungin at 0.1 mug/ml and 0.05 mug/ml to the macrophage cultures increased antifungal activity. The growth inhibition by the combination was significantly greater than drug alone (P < .01) and MDM alone (P < .01). There was no significant interference with or enhancement of PMNs and caspofungin. These data support the activity of caspofungin against A. fumigatus in vitro, and indicates a cooperative activity with human effector cells. This suggests caspofungin in vivo would have increased efficacy as it combines with host defenses against A. fumigatus. (C) 2001 Elsevier Science Inc. All rights reserved.