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Open AccessArticle

Phospholipid Arachidonic Acid Remodeling During Phagocytosis in Mouse Peritoneal Macrophages

1
Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Valladolid, 47003 Valladolid, Spain
2
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 28029 Madrid, Spain
3
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
*
Author to whom correspondence should be addressed.
Present address: Center of Childhood Cancer Center, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Biomedicines 2020, 8(8), 274; https://doi.org/10.3390/biomedicines8080274
Received: 8 July 2020 / Revised: 30 July 2020 / Accepted: 3 August 2020 / Published: 5 August 2020
(This article belongs to the Section Molecular and Translational Medicine)
Macrophages contain large amounts of arachidonic acid (AA), which distributes differentially across membrane phospholipids. This is largely due to the action of coenzyme A-independent transacylase (CoA-IT), which transfers the AA primarily from diacyl choline-containing phospholipids to ethanolamine-containing phospholipids. In this work we have comparatively analyzed glycerophospholipid changes leading to AA mobilization in mouse peritoneal macrophages responding to either zymosan or serum-opsonized zymosan (OpZ). These two phagocytic stimuli promote the cytosolic phospholipase A2-dependent mobilization of AA by activating distinct surface receptors. Application of mass spectrometry-based lipid profiling to identify changes in AA-containing phospholipids during macrophage exposure to both stimuli revealed significant decreases in the levels of all major choline phospholipid molecular species and a major phosphatidylinositol species. Importantly, while no changes in ethanolamine phospholipid species were detected on stimulation with zymosan, significant decreases in these species were observed when OpZ was used. Analyses of CoA-IT-mediated AA remodeling revealed that the process occurred faster in the zymosan-stimulated cells compared with OpZ-stimulated cells. Pharmacological inhibition of CoA-IT strongly blunted AA release in response to zymosan but had only a moderate effect on the OpZ-mediated response. These results suggest a hitherto undescribed receptor-dependent role for CoA-independent AA remodeling reactions in modulating the eicosanoid biosynthetic response of macrophages. Our data help define novel targets within the AA remodeling pathway with potential use to control lipid mediator formation View Full-Text
Keywords: arachidonic acid; eicosanoids; phospholipid remodeling; phospholipase A2; inflammation; monocytes/macrophages arachidonic acid; eicosanoids; phospholipid remodeling; phospholipase A2; inflammation; monocytes/macrophages
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Gil-de-Gómez, L.; Monge, P.; Rodríguez, J.P.; Astudillo, A.M.; Balboa, M.A.; Balsinde, J. Phospholipid Arachidonic Acid Remodeling During Phagocytosis in Mouse Peritoneal Macrophages. Biomedicines 2020, 8, 274.

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