Alpha-linolenic acid enhances the phagocytic and secretory functions of alternatively activated macrophages in part via changes to the oxylipin profile. (February 2020)

• Record Type: Journal Article
• Authors: Pauls, Samantha D.; Rodway, Lisa A.; Winter, Tanja; Taylor, Carla G.; Zahradka, Peter; Aukema, Harold M.
• Is Part Of: International journal of biochemistry & cell biology. Volume 119(2020)
• Publication Date: 2020-02
• Subjects: AA arachidonic acid -- ALA α-linolenic acid -- COX cyclooxygenase -- CYPE cytochrome P450 epoxygenase -- CYPH cytochrome P450 hydrolase -- DGLA dihomo-gamma-linolenic acid -- dh dihydro -- dhk dihydroketo -- DiHDoHE dihydroxy-docosahexaenoic acid -- DiHDPE dihydroxy-docosapentaenoic acid -- DiHETrE dihydroxy-eicosatrienoic acid -- DiHOME dihydroxy-octadecenoic acid -- EPA eicosapentaenoic acid -- EpDPE epoxy-eicosadocosapentaenoic acid -- EpETE epoxy-eicosatetraenoic acid -- EpETrE epoxy-eicosatrienoic acid -- EpODE epoxy-eicosadienoic acid -- EpOME epoxy-octadecenoic acid -- FA fatty acid -- GLA gamma-linolenic acid -- HDoHE hydroxy-docosahexaenoic acid -- HEPE hydroxy-eicosapentaenoic acid -- HETE hydroxy-eicosatetraenoic acid -- HETrE hydroxy-eicosatrienoic acid -- HHTrE hydroxy-heptadecatrienoic acid -- HODE hydroxy-octadecadienoic acid -- HOTrE hydroxy-octadecatrienoic acid -- IL interkeukin -- k keto -- LA linoleic acid -- LOX lipoxygenase -- LPS lipopolysaccharide -- OA oleic acid -- oxoEDE oxo-eicosadienoic acid -- oxoETE oxo-eicosatetraenoic acid -- oxoODE oxo-octadecadienoic acid -- oxoOTrE oxo-octadecatrienoic acid -- PG prostaglandin -- PLA2 phospholipase A2 -- tet tetranor -- TriHOME trihydroxy-octadecenoic acid -- TX thromboxane; Macrophage -- Inflammation -- α-linolenic acid -- Oxylipins -- Phospholipase A2; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2019.105662
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: Alternatively activated macrophages are innate immune cells that contribute to resolution of inflammation and maintenance of homeostasis. Modulation of available fatty acid sources is thought to affect cellular physiology through a variety of mechanisms, including through alterations to the profile of oxygenated free fatty acid metabolites, called oxylipins, produced in a cell type specific manner. Here, we investigated how treatment with the plant-sourced omega-3 fatty acid α-linolenic acid (ALA) affects the oxylipin profile and functional capacity of a cell culture model of human alternatively activated (M2a-like) macrophages. In a targeted but unbiased screen, ALA enhanced the production of oxylipins from all polyunsaturated fatty acid (PUFA) precursors, with oxylipins derived from ALA being enhanced the most. Consistently, ALA treatment enhanced the expression of both cytoplasmic and calcium-independent phospholipase A2. At a functional level, ALA treatment increased phagocytic activity and altered production of the chemokine MCP-1 by M2a-like cells in a manner dependent on the time of treatment. ALA treatment during polarization increased MCP-1 secretion, which was sensitive to pharmacological inhibition of 15-LOX-1 by ML351. Thus, ALA modulates the phenotype of alternatively activated macrophages, likely through its own LOX-derived oxylipins and/or through general modulation of oxylipin biosynthesis. These effects likely contribute to the overall anti-inflammatory benefit observed with ALA supplementation.