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

Author(s)

Sorgi, Carlos A. ; Zarini, Simona ; Martin, Sarah A. ; Sanchez, Raphael L. ; Scandiuzzi, Rodrigo F. ; Gijon, Miguel A. ; Guijas, Carlos ; Flamand, Nicolas ; Murphy, Robert C. ; Faccioli, Lucia H.

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 7, SEP 8 2017.
• Web of Science Citations: 9

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-2, prostaglandin (PG) E-2, and PGD(2) 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 PGE2/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. (AU)

• FAPESP's process: 14/07125-6 - New functional aspects of eicosanoids
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/13127-1 - The role of nuclear 5-Lipoxygenase and leukotrienes on macrophage inflammatory genes regulation
• Grantee: Carlos Arterio Sorgi
• Support Opportunities: Scholarships abroad - Research
• FAPESP's process: 15/00658-1 - New functional aspects of eicosanoids
• Grantee: Lúcia Helena Faccioli
• Support Opportunities: Multi-user Equipment Program