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...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2016-07, Vol.291 (27), p.13964-13973
Main Authors: 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
Format: Article
Language:English
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)
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M115.695866