Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity
Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity
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DOI：
10.1074/jbc.m115.695866
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发表时间：
2016-07-01
影响因子：
4.8
通讯作者：
Nizet, Victor
中科院分区：
文献类型：
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作者：
Hollands, Andrew;Corriden, Ross;Nizet, Victor
病原菌中出现的抗生素耐药性是一个具有重要临床意义的问题，迫切需要新的治疗方法。腰果酸是腰果壳提取物的主要活性成分，是一种天然产品，用于治疗各种疾病，包括感染性腹泻。在这里，我们研究这种天然产物对人类中性粒细胞功能的影响。我们发现，漆树酸刺激生产活性氧和中性粒细胞胞外陷阱，两种机制利用中性粒细胞杀死入侵的细菌。分子建模和药理学抑制剂研究表明，漆树酸通过激活表面表达的G蛋白偶联鞘氨醇-1-磷酸受体，以PI 3 K依赖性方式刺激中性粒细胞。响应于漆树酸产生的神经元胞外陷阱是杀菌的，并且补充化合物的选择直接抗微生物活性。
Emerging antibiotic resistance among pathogenic bacteria is an issue of great clinical importance, and new approaches to therapy are urgently needed. Anacardic acid, the primary active component of cashew nut shell extract, is a natural product used in the treatment of a variety of medical conditions, including infectious abscesses. Here, we investigate the effects of this natural product on the function of human neutrophils. We find that anacardic acid stimulates the production of reactive oxygen species and neutrophil extracellular traps, two mechanisms utilized by neutrophils to kill invading bacteria. Molecular modeling and pharmacological inhibitor studies suggest anacardic acid stimulation of neutrophils occurs in a PI3K-dependent manner through activation of surface-expressed G protein-coupled sphingosine-1-phosphate receptors. Neutrophil extracellular traps produced in response to anacardic acid are bactericidal and complement select direct antimicrobial activities of the compound.