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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Biochim+Biophys+Acta
2015 ; 1851
(4
): 397-413
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Protectins and maresins: New pro-resolving families of mediators in acute
inflammation and resolution bioactive metabolome
#MMPMID25139562
Serhan CN
; Dalli J
; Colas RA
; Winkler JW
; Chiang N
Biochim Biophys Acta
2015[Apr]; 1851
(4
): 397-413
PMID25139562
show ga
Acute inflammatory responses are protective, yet without timely resolution can
lead to chronic inflammation and organ fibrosis. A systems approach to
investigate self-limited (self-resolving) inflammatory exudates in mice and
structural elucidation uncovered novel resolution phase mediators in vivo that
stimulate endogenous resolution mechanisms in inflammation. Resolving
inflammatory exudates and human leukocytes utilize DHA and other n-3 EFA to
produce three structurally distinct families of potent di- and
trihydroxy-containing products, with several stereospecific potent mediators in
each family. Given their potent and stereoselective picogram actions, specific
members of these new families of mediators from the DHA metabolome were named
D-series resolvins (Resolvin D1 to Resolvin D6), protectins (including protectin
D1-neuroprotectin D1), and maresins (MaR1 and MaR2). In this review, we focus on
a) biosynthesis of protectins and maresins as anti-inflammatory-pro-resolving
mediators; b) their complete stereochemical assignments and actions in vivo in
disease models. Each pathway involves the biosynthesis of epoxide-containing
intermediates produced from hydroperoxy-containing precursors from human
leukocytes and within exudates. Also, aspirin triggers an endogenous DHA
metabolome that biosynthesizes potent products in inflammatory exudates and human
leukocytes, namely aspirin-triggered Neuroprotectin D1/Protectin D1
[AT-(NPD1/PD1)]. Identification and structural elucidation of these new families
of bioactive mediators in resolution has opened the possibility of diverse
patho-physiologic actions in several processes including infection, inflammatory
pain, tissue regeneration, neuroprotection-neurodegenerative disorders, wound
healing, and others. This article is part of a Special Issue entitled "Oxygenated
metabolism of PUFA: analysis and biological relevance".