Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity
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 condition...
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| Veröffentlicht in: | The Journal of biological chemistry 2016-07, Vol.291 (27), p.13964-13973 |
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| container_title | The Journal of biological chemistry |
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| creator | Hollands, Andrew Corriden, Ross Gysler, Gabriela Dahesh, Samira Olson, Joshua Raza Ali, Syed Kunkel, Maya T. Lin, Ann E. Forli, Stefano Newton, Alexandra C. Kumar, Geetha B. Nair, Bipin G. Perry, J.Jefferson P. Nizet, Victor |
| description | 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. |
| doi_str_mv | 10.1074/jbc.M115.695866 |
| format | Article |
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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.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M115.695866</identifier><identifier>PMID: 27226531</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Anacardic Acid ; Anacardic Acids - pharmacology ; Anacardium - chemistry ; Anti-Bacterial Agents - pharmacology ; antibiotic resistance ; Extracellular Traps - metabolism ; Humans ; Immunology ; innate immunity ; Lysophospholipids - metabolism ; neutrophil ; Neutrophil extracellular traps ; Neutrophils - drug effects ; PI3 kinase ; reactive oxygen species (ROS) ; Respiratory Burst ; Sphingosine - analogs & derivatives ; Sphingosine - metabolism ; sphingosine-1-phosphate (S1P)</subject><ispartof>The Journal of biological chemistry, 2016-07, Vol.291 (27), p.13964-13973</ispartof><rights>2016 © 2016 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2016 by The American Society for Biochemistry and Molecular Biology, Inc.</rights><rights>2016 by The American Society for Biochemistry and Molecular Biology, Inc. 2016 The American Society for Biochemistry and Molecular Biology, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c555t-f457506c796247faca0886d82b1930b75643f0175cabf56f089001745982a6333</citedby><cites>FETCH-LOGICAL-c555t-f457506c796247faca0886d82b1930b75643f0175cabf56f089001745982a6333</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933157/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933157/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27226531$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hollands, Andrew</creatorcontrib><creatorcontrib>Corriden, Ross</creatorcontrib><creatorcontrib>Gysler, Gabriela</creatorcontrib><creatorcontrib>Dahesh, Samira</creatorcontrib><creatorcontrib>Olson, Joshua</creatorcontrib><creatorcontrib>Raza Ali, Syed</creatorcontrib><creatorcontrib>Kunkel, Maya T.</creatorcontrib><creatorcontrib>Lin, Ann E.</creatorcontrib><creatorcontrib>Forli, Stefano</creatorcontrib><creatorcontrib>Newton, Alexandra C.</creatorcontrib><creatorcontrib>Kumar, Geetha B.</creatorcontrib><creatorcontrib>Nair, Bipin G.</creatorcontrib><creatorcontrib>Perry, J.Jefferson P.</creatorcontrib><creatorcontrib>Nizet, Victor</creatorcontrib><title>Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>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.</description><subject>Anacardic Acid</subject><subject>Anacardic Acids - pharmacology</subject><subject>Anacardium - chemistry</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>antibiotic resistance</subject><subject>Extracellular Traps - metabolism</subject><subject>Humans</subject><subject>Immunology</subject><subject>innate immunity</subject><subject>Lysophospholipids - metabolism</subject><subject>neutrophil</subject><subject>Neutrophil extracellular traps</subject><subject>Neutrophils - drug effects</subject><subject>PI3 kinase</subject><subject>reactive oxygen species (ROS)</subject><subject>Respiratory Burst</subject><subject>Sphingosine - analogs & derivatives</subject><subject>Sphingosine - metabolism</subject><subject>sphingosine-1-phosphate (S1P)</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1PHCEYxonR1NX27M1w9DIrHwMDF5PtxlYT3TZRE2-EYRgXMzNsgdnWs_-4bFaNHsqF8L4Pv_eBB4AjjKYYVeXpY22m1xizKZdMcL4DJhgJWlCG73fBBCGCC0mY2AcHMT6ivEqJv4B9UhHCGcUT8LzQaQy6g7-Db0aT4GzQRofGGTgzroFt8D2c67i0f-FiTPBmabsuwpvk-rHTyUa4sGMKfrV0HTz_l4I2WZBbAd4GvXrDOj9APTTwuzbJBpfJeeQs19cuPX0Fe63uov32uh-Cux_nt_OL4urXz8v57KowjLFUtCWrGOKmkpyUVZttIiF4I0iNJUV1xXhJW4QrZnTdMt4iIVE-lkwKojml9BCcbbmrse5tY-yQ7XZqFVyvw5Py2qnPncEt1YNfq1JSilmVASevgOD_jDYm1bu4ea8erB-jwgLhknAqRZaebqUm-BiDbd_HYKQ20akcndpEp7bR5RvHH92969-yygK5Fdj8R2tng4rG2cHYxgVrkmq8-y_8BXPjqlc</recordid><startdate>20160701</startdate><enddate>20160701</enddate><creator>Hollands, Andrew</creator><creator>Corriden, Ross</creator><creator>Gysler, Gabriela</creator><creator>Dahesh, Samira</creator><creator>Olson, Joshua</creator><creator>Raza Ali, Syed</creator><creator>Kunkel, Maya T.</creator><creator>Lin, Ann E.</creator><creator>Forli, Stefano</creator><creator>Newton, Alexandra C.</creator><creator>Kumar, Geetha B.</creator><creator>Nair, Bipin G.</creator><creator>Perry, J.Jefferson P.</creator><creator>Nizet, Victor</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160701</creationdate><title>Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity</title><author>Hollands, Andrew ; 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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Anacardic Acid Anacardic Acids - pharmacology Anacardium - chemistry Anti-Bacterial Agents - pharmacology antibiotic resistance Extracellular Traps - metabolism Humans Immunology innate immunity Lysophospholipids - metabolism neutrophil Neutrophil extracellular traps Neutrophils - drug effects PI3 kinase reactive oxygen species (ROS) Respiratory Burst Sphingosine - analogs & derivatives Sphingosine - metabolism sphingosine-1-phosphate (S1P) |
| title | Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity |
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