Dormant 5-lipoxygenase in inflammatory macrophages is triggered by exogenous arachidonic acid.

TitleDormant 5-lipoxygenase in inflammatory macrophages is triggered by exogenous arachidonic acid.
Publication TypeJournal Article
Year of Publication2017
AuteursSorgi, CA, Zarini, S, Martin, SA, Sanchez, RL, Scandiuzzi, RF, Gijón, MA, Guijas, C, Flamand, N, Murphy, RC, Faccioli, LH
JournalSci Rep
Volume7
Issue1
Pagination10981
Date Published2017 09 08
ISSN2045-2322
KeywordsAnimals, Arachidonate 5-Lipoxygenase, Arachidonic Acid, Bone Marrow Cells, Cells, Cultured, Chromatography, High Pressure Liquid, Cyclic AMP, Eicosanoids, Female, Gene Expression Regulation, Lipopolysaccharides, Lipoxygenase, Macrophages, Male, Mice, Phospholipids, Signal Transduction, Tandem Mass Spectrometry
Abstract

The differentiation of resident tissue macrophages from embryonic precursors and that of inflammatory macrophages from bone marrow cells leads to macrophage heterogeneity. Further plasticity is displayed through their ability to be polarized as subtypes M1 and M2 in a cell culture microenvironment. However, the detailed regulation of eicosanoid production and its involvement in macrophage biology remains unclear. Using a lipidomics approach, we demonstrated that eicosanoid production profiles between bone marrow-derived (BMDM) and peritoneal macrophages differed drastically. In polarized BMDMs, M1 and M2 phenotypes were distinguished by thromboxane B, prostaglandin (PG) E, and PGD production, in addition to lysophospholipid acyltransferase activity. Although Alox5 expression and the presence of 5-lipoxygenase (5-LO) protein in BMDMs was observed, the absence of leukotrienes production reflected an impairment in 5-LO activity, which could be triggered by addition of exogenous arachidonic acid (AA). The BMDM 5-LO regulatory mechanism was not responsive to PGE/cAMP pathway modulation; however, treatment to reduce glutathione peroxidase activity increased 5-LO metabolite production after AA stimulation. Understanding the relationship between the eicosanoids pathway and macrophage biology may offer novel strategies for macrophage-associated disease therapy.

DOI10.1038/s41598-017-11496-3
Alternate JournalSci Rep
PubMed ID28887514
PubMed Central IDPMC5591212
Grant ListF31 NS080486 / NS / NINDS NIH HHS / United States
U54 HL117798 / HL / NHLBI NIH HHS / United States