Abstract
Macrophages have diverse functions in the pathogenesis, resolution, and repair of inflammatory processes. Elegant studies have elucidated the metabolomic and transcriptomic profiles of activated macrophages. However, the versatility of macrophage responses in inflammation is likely due, at least in part, to their ability to rearrange their repertoire of bioactive lipids, including fatty acids and oxylipins. This review will describe the fatty acids and oxylipins generated by macrophages and their role in type 1 and type 2 immune responses. We will highlight lipidomic studies that have shaped the current understanding of the role of lipids in macrophage polarization.
Highlights
In a model of nonalcoholic steatohepatitis induced by methionine- and choline-deficient diet, administration of PdA reduced ceroid-laden macrophages
Since the first comprehensive lipid analysis of mouse macrophages [18], the availability of lipid mass spectrometry has drastically expanded the studies on lipid functions related to the many faces of macrophage activation in health and disease
The identification of bioactive lipids produced by macrophages in various conditions has improved our understanding of the role of lipids in the pathogenesis of many diseases
Summary
Immune Responses: From Fatty Acids to Oxylipins. Molecules 2022, 27, 152. Macrophages are a rich source of bioactive lipids, including fatty acids (FAs) and their oxygenated metabolites oxylipins. FAs may act directly at cognate receptors in an autocrine or paracrine fashion They can bind specific G-protein-coupled receptors (GPCRs), including free fatty acid receptors (FFARs) and GPR84, expressed on macrophages and target cells [6,7,8], serving as signaling molecules [9,10]. FAs serve multiple purposes in the cell: they contribute to the membrane structure; they are a source of energy; and they are second messengers and signaling molecules in immune responses, directly or indirectly through the generation of oxylipins. This review will summarize FAs and derived oxylipins produced by macrophages as revealed by comprehensive lipidomic studies and we will correlate them with the functions of M1 and M2 macrophages in type 1 and type 2 immune responses
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