Eosinophils synthesize trihydroxyoctadecenoic acids (TriHOMEs) via a 15-lipoxygenase dependent process

Publication date: Available online 7 January 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of LipidsAuthor(s): David Fuchs, Xiao Tang, Anna-Karin Johnsson, Sven-Erik Dahlén, Mats Hamberg, Craig E. WheelockAbstractTrihydroxyoctadecenoic acids (TriHOMEs) are linoleic acid-derived lipid mediators reported to be dysregulated in obstructive lung disease. In contrast to many other oxylipins, TriHOME biosynthesis in humans is still poorly understood. The association of TriHOMEs with inflammation prompted the current investigation into the ability of human granulocytes to synthesize the 16 different 9,10,13-TriHOME and 9,12,13-TriHOME isomers and of the TriHOME biosynthetic pathway. Following incubation with linoleic acid, eosinophils and (to a lesser extent) the mast cell line LAD2, but not neutrophils, formed TriHOMEs. Stereochemical analysis revealed that TriHOMEs produced by eosinophils predominantly evidenced the 13(S) configuration, suggesting 15-lipoxygenase (15-LOX)-mediated synthesis. TriHOME formation was blocked following incubation with the 15-LOX inhibitor BXL-3887 and was shown to be largely independent of soluble epoxide hydrolase and cytochrome P450 activities. TriHOME synthesis was abolished when linoleic acid was replaced with 13-HODE, but increased in incubations with 13-HpODE, indicating the intermediary role of epoxy alcohols in TriHOME formation. In contrast to eosinophils, LAD2 cells formed TriHOMEs having predominantly the 13(R)...
Source: Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids - Category: Lipidology Source Type: research