The macrocyclic lactone anthelmintics are the only class of drug currently used to prevent heartworm disease. Their extremely high potency in vivo is not mirrored by their activity against Dirofilaria immitis larvae in vitro, leading to suggestions that they may require host immune functions to kill the parasites. We have previously shown that ivermectin stimulates the binding of canine peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes (PMNs) to D. immitis microfilariae (Mf). We have now extended these studies to moxidectin and examined the ability of both drugs to stimulate canine PBMC and PMN attachment to Mf from multiple strains of D. immitis, including two that are proven to be resistant to ivermectin in vivo. Both ivermectin and moxidectin significantly increased the percentage of drug-susceptible parasites with cells attached at very low concentrations (<10 nM), but much higher concentrations of ivermectin (>100 nM) were required to increase the percentage of the two resistant strains, Yazoo-2013 and Metairie-2014, with cells attached. Moxidectin increased the percentage of the two resistant strains with cells attached at lower concentrations (<10 nM) than did ivermectin. The attachment of the PBMCs and PMNs did not result in any parasite killing in vitro. These data support the biological relevance of the drug-stimulated attachment of canine leukocytes to D. immitis Mf and suggest that this phenomenon is related to the drug resistance status of the parasites.

中文翻译：

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大环内酯驱虫药诱导的白细胞与微丝fil虫的结合：对寄生虫耐药性的影响。

大环内酯驱虫药是目前用于预防丝虫病的唯一药物。它们在体内的极高效力不能通过其体外对敌对丝虫病幼虫的活性来反映，这提示它们可能需要宿主免疫功能才能杀死寄生虫。先前我们已经表明，伊维菌素刺激犬外周血单核细胞（PBMC）和多形核白细胞（PMN）与D. immitis microfilariae（Mf）的结合。现在，我们将这些研究扩展到莫昔克丁，并研究了两种药物刺激多种D. immitis菌株刺激犬PBMC和PMN附着于Mf的能力，其中包括两种在体内被证明对伊维菌素具有抗性的药物。伊维菌素和莫西菌素都显着增加了细胞附着的非常低浓度（<10 nM）的药物敏感性寄生虫的百分比，但是需要更高浓度的伊维菌素（> 100 nM）来增加两种耐药菌株Yazoo的百分比-2013和Metairie-2014，带有细胞。与依维菌素相比，莫昔克丁增加了两个较低浓度（<10 nM）细胞附着的抗性菌株的百分比。PBMC和PMN的附着不会导致体外任何寄生虫杀死。这些数据支持了药物刺激的犬白细胞与D. Immitis Mf的生物学相关性，并表明该现象与寄生虫的耐药性有关。但是需要更高浓度的伊维菌素（> 100 nM）才能增加两种抗性菌株Yazoo-2013和Metairie-2014的细胞附着率。与依维菌素相比，莫昔克丁增加了两个较低浓度（<10 nM）细胞附着的抗性菌株的百分比。PBMC和PMN的附着不会导致体外任何寄生虫杀死。这些数据支持了药物刺激的犬白细胞与D. Immitis Mf的生物学相关性，并表明该现象与寄生虫的耐药性有关。但是需要更高浓度的伊维菌素（> 100 nM）才能增加两种抗性菌株Yazoo-2013和Metairie-2014的细胞附着率。与依维菌素相比，莫昔克丁增加了两个较低浓度（<10 nM）细胞附着的抗性菌株的百分比。PBMC和PMN的附着不会导致体外任何寄生虫杀死。这些数据支持了药物刺激的犬白细胞与D. Immitis Mf的生物学相关性，并表明该现象与寄生虫的耐药性有关。与依维菌素相比，莫昔克丁增加了两个较低浓度（<10 nM）细胞附着的抗性菌株的百分比。PBMC和PMN的附着不会导致体外任何寄生虫杀死。这些数据支持了药物刺激的犬白细胞与D. Immitis Mf的生物学相关性，并表明该现象与寄生虫的耐药性有关。与依维菌素相比，莫昔克丁增加了两个较低浓度（<10 nM）细胞附着的抗性菌株的百分比。PBMC和PMN的附着不会导致体外任何寄生虫杀死。这些数据支持了药物刺激的犬白细胞与D. Immitis Mf的生物学相关性，并表明该现象与寄生虫的耐药性有关。