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. 2020 Aug 8;8:129. doi: 10.1186/s40478-020-00989-4

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — LT biosynthesis is part of metabolism of the omega 6 polyunsaturated arachidonic acid (AA), which is cleaved from plasmamembranes by phospholipase A₂ (PLA₂). AA is a substrate for several lipoxygenases. For the production of LTs it is first converted into 5-hydroxy-peroxy-eicosatetraenoic acid (5-HPETE) and afterwards into LTA4, both steps mediated by a complex of the enzyme 5-lipoxygenase (5-Lox) and 5-lipoxygenase activating protein (FLAP) [22]. From LTA4 arise either Leukotriene B4 (LTB4) formed by epoxide hydrolase or Leukotriene C4 (LTC4) formed by LTC4 synthase, which can be further metabolized to LTD4 and LTE4 [23]. LTC4, LTD4 and LTE4 are summarized under the term cysteinyl-leukotrienes (CysLTs). CysLTs display different affinities towards the receptors cysteinyl-leukotriene receptor 1 and 2 (CysLT1R [24]), CysLT2R [25]) and G-protein coupled receptor 17 (GPR17 [26, 27]). The enzyme 5-Lox is also involved in some steps of biosynthesis of specialized pro-resolving mediators from omega 3 poly-unsaturated fatty acids (DHA – docosahexaenoic acid; EPA – eicosapentaenoic acid)