TY  - JOUR
A1  - Schebb, Nils Helge
A1  - Kühn, Hartmut
A1  - Kahnt, Astrid Stefanie
A1  - Rund, Katharina M.
A1  - O’Donnell, Valerie B.
A1  - Flamand, Nicolas
A1  - Peters-Golden, Marc
A1  - Jakobsson, Per-Johan
A1  - Weylandt, Karsten-Henrich
A1  - Rohwer, Nadine
A1  - Murphy, Robert C.
A1  - Geisslinger, Gerd
A1  - FitzGerald, Garret A.
A1  - Hanson, Julien
A1  - Dahlgren, Claes
A1  - Alnouri, Mohamad Wessam
A1  - Offermanns, Stefan
A1  - Steinhilber, Dieter
T1  - Formation, signaling and occurrence of specialized pro-resolving lipid mediators - what is the evidence so far?
T2  - Frontiers in pharmacology
N2  - Formation of specialized pro-resolving lipid mediators (SPMs) such as lipoxins or resolvins usually involves arachidonic acid 5-lipoxygenase (5-LO, ALOX5) and different types of arachidonic acid 12- and 15-lipoxygenating paralogues (15-LO1, ALOX15; 15-LO2, ALOX15B; 12-LO, ALOX12). Typically, SPMs are thought to be formed via consecutive steps of oxidation of polyenoic fatty acids such as arachidonic acid, eicosapentaenoic acid or docosahexaenoic acid. One hallmark of SPM formation is that reported levels of these lipid mediators are much lower than typical pro-inflammatory mediators including the monohydroxylated fatty acid derivatives (e.g., 5-HETE), leukotrienes or certain cyclooxygenase-derived prostaglandins. Thus, reliable detection and quantification of these metabolites is challenging. This paper is aimed at critically evaluating i) the proposed biosynthetic pathways of SPM formation, ii) the current knowledge on SPM receptors and their signaling cascades and iii) the analytical methods used to quantify these pro-resolving mediators in the context of their instability and their low concentrations. Based on current literature it can be concluded that i) there is at most, a low biosynthetic capacity for SPMs in human leukocytes. ii) The identity and the signaling of the proposed G-protein-coupled SPM receptors have not been supported by studies in knock-out mice and remain to be validated. iii) In humans, SPM levels were neither related to dietary supplementation with their ω-3 polyunsaturated fatty acid precursors nor were they formed during the resolution phase of an evoked inflammatory response. iv) The reported low SPM levels cannot be reliably quantified by means of the most commonly reported methodology. Overall, these questions regarding formation, signaling and occurrence of SPMs challenge their role as endogenous mediators of the resolution of inflammation.
KW  - lipoxygenase
KW  - SPM
KW  - lipoxin
KW  - resolvin
KW  - resolution of inflammation
KW  - leukotriene
KW  - FPR
KW  - LC-MS-based lipid mediator analysis
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73937
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-739372
SN  - 1663-9812
VL  - 13
IS  - art. 838782
SP  - 1
EP  - 22
PB  - Frontiers Media
CY  - Lausanne
ER  -