@article{3001915,
    title = "Cytosolic group IVA and calcium-independent group VIA phospholipase A2s act on distinct phospholipid pools in zymosan-stimulated mouse peritoneal macrophages",
    author = "Gil-De-Gómez, L. and Astudillo, A.M. and Guijas, C. and Magrioti, V. and Kokotos, G. and Balboa, M.A. and Balsinde, J.",
    journal = "Journal of Immunological Methods",
    year = "2014",
    volume = "192",
    number = "2",
    pages = "752-762",
    issn = "0022-1759",
    doi = "10.4049/jimmunol.1302267",
    keywords = "arachidonic acid;  glycerophosphorylcholine derivative;  lysophospholipid;  palmitoyl glycerophosphocholine;  phospholipase A2 group IV;  phospholipase A2 group IVA;  phospholipase A2 group VI;  phospholipase A2 group VIA;  phospholipid;  stearoyl glycerophosphocholine;  unclassified drug;  zymosan, article;  cell stimulation;  cytosol;  enzyme activity;  enzyme specificity;  immunostimulation;  innate immunity;  lipid analysis;  lipid composition;  lipid hydrolysis;  lipogenesis;  macrophage activation;  mass spectrometry;  peritoneum macrophage;  priority journal, Animals;  Arachidonic Acid;  Calcium;  Cells, Cultured;  Cytosol;  Group IV Phospholipases A2;  Group VI Phospholipases A2;  Macrophages, Peritoneal;  Male;  Mice;  Zymosan",
    abstract = "Phospholipase A2s generate lipid mediators that constitute an important component of the integrated response of macrophages to stimuli of the innate immune response. Because these cells contain multiple phospholipase A2 forms, the challenge is to elucidate the roles that each of these forms plays in regulating normal cellular processes and in disease pathogenesis. A major issue is to precisely determine the phospholipid substrates that these enzymes use for generating lipid mediators. There is compelling evidence that group IVA cytosolic phospholipase A2 (cPLA2α) targets arachidonic acid-containing phospholipids but the role of the other cytosolic enzyme present in macrophages, the Ca2+-independent group VIA phospholipase A2 (iPLA2β) has not been clearly defined. We applied mass spectrometry-based lipid profiling to study the substrate specificities of these two enzymes during inflammatory activation of macrophages with zymosan. Using selective inhibitors, we find that, contrary to cPLA2α, iPLA2β spares arachidonate-containing phospholipids and hydrolyzes only those that do not contain arachidonate. Analyses of the lysophospholipids generated during activation reveal that one of the major species produced, palmitoyl-glycerophosphocholine, is generated by iPLA2β, with minimal or no involvement of cPLA 2α. The other major species produced, stearoyl- glycerophosphocholine, is generated primarily by cPLA2α. Collectively, these findings suggest that cPLA2α and iPLA 2β act on different phospholipids during zymosan stimulation of macrophages and that iPLA2β shows a hitherto unrecognized preference for choline phospholipids containing palmitic acid at the sn-1 position that could be exploited for the design of selective inhibitors of this enzyme with therapeutic potential. Copyright © 2014 by The American Association of Immunologists, Inc."
}