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Open AccessFeature PaperArticle

A Lipidomic Perspective of the Action of Group IIA Secreted Phospholipase A2 on Human Monocytes: Lipid Droplet Biogenesis and Activation of Cytosolic Phospholipase A2α

1
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Valladolid, 47003 Valladolid, Spain
2
Laboratorio de Investigaciones Bioquímicas de la Facultad de Medicina (LIBIM), Instituto de Química Básica y Aplicada del Nordeste Argentino (IQUIBA-NEA), Universidad Nacional del Nordeste, Consejo Nacional de Investigaciones Científicas y Técnicas (UNNE-CONICET), Corrientes 3400, Argentina
3
Laboratorio de Farmacologia, Instituto Butantan, Sao Paulo 01000, Brazil
4
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029 Madrid, Spain
5
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José 11501–2060, Costa Rica
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2020, 10(6), 891; https://doi.org/10.3390/biom10060891
Received: 14 May 2020 / Revised: 8 June 2020 / Accepted: 10 June 2020 / Published: 10 June 2020
(This article belongs to the Special Issue Phospholipases: From Structure to Biological Function)
Phospholipase A2s constitute a wide group of lipid-modifying enzymes which display a variety of functions in innate immune responses. In this work, we utilized mass spectrometry-based lipidomic approaches to investigate the action of Asp-49 Ca2+-dependent secreted phospholipase A2 (sPLA2) (MT-III) and Lys-49 sPLA2 (MT-II), two group IIA phospholipase A2s isolated from the venom of the snake Bothrops asper, on human peripheral blood monocytes. MT-III is catalytically active, whereas MT-II lacks enzyme activity. A large decrease in the fatty acid content of membrane phospholipids was detected in MT III-treated monocytes. The significant diminution of the cellular content of phospholipid-bound arachidonic acid seemed to be mediated, in part, by the activation of the endogenous group IVA cytosolic phospholipase A2α. MT-III triggered the formation of triacylglycerol and cholesterol enriched in palmitic, stearic, and oleic acids, but not arachidonic acid, along with an increase in lipid droplet synthesis. Additionally, it was shown that the increased availability of arachidonic acid arising from phospholipid hydrolysis promoted abundant eicosanoid synthesis. The inactive form, MT-II, failed to produce any of the effects described above. These studies provide a complete lipidomic characterization of the monocyte response to snake venom group IIA phospholipase A2, and reveal significant connections among lipid droplet biogenesis, cell signaling and biochemical pathways that contribute to initiating the inflammatory response. View Full-Text
Keywords: phospholipase A2; lipidomics; mass spectrometry; lipid signaling; inflammation; monocytes/macrophages phospholipase A2; lipidomics; mass spectrometry; lipid signaling; inflammation; monocytes/macrophages
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MDPI and ACS Style

Rodríguez, J.P.; Leiguez, E.; Guijas, C.; Lomonte, B.; Gutiérrez, J.M.; Teixeira, C.; Balboa, M.A.; Balsinde, J. A Lipidomic Perspective of the Action of Group IIA Secreted Phospholipase A2 on Human Monocytes: Lipid Droplet Biogenesis and Activation of Cytosolic Phospholipase A2α. Biomolecules 2020, 10, 891.

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