Document Detail


Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation.
MedLine Citation:
PMID:  21206090     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
E-series resolvins are antiinflammatory and pro-resolving lipid mediators derived from the ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) that actively clear inflammation to promote tissue homeostasis. Aspirin, in addition to exerting antithrombotic actions, also triggers the biosynthesis of these specialized pro-resolving mediators. Here, we used metabolomic profiling to investigate the biosynthesis of E-series resolvins with specific chiral chemistry in serum from human subjects and present evidence for new 18S series resolvins. Aspirin increased endogenous formation of 18S-hydroxyeicosapentaenoate (18S-HEPE) compared with 18R-HEPE, a known resolvin precursor. Human recombinant 5-lipoxygenase used both enantiomers as substrates, and recombinant LTA4 hydrolase (LTA4H) converted chiral 5S(6)-epoxide-containing intermediates to resolvin E1 and 18S-resolvin E1 (RvE1 and 18S-RvE1, respectively). 18S-RvE1 bound to the leukocyte GPCRs ChemR23 and BLT1 with increased affinity and potency compared with the R-epimer, but was more rapidly inactivated than RvE1 by dehydrogenase. Like RvE1, 18S-RvE1 enhanced macrophage phagocytosis of zymosan, E. coli, and apoptotic neutrophils and reduced both neutrophil infiltration and proinflammatory cytokines in murine peritonitis. These results demonstrate two parallel stereospecific pathways in the biosynthesis of E-series resolvins, 18R- and 18S-, which are antiinflammatory, pro-resolving, and non-phlogistic and may contribute to the beneficial actions of aspirin and ω-3 polyunsaturated fatty acids.
Authors:
Sungwhan F Oh; Padmini S Pillai; Antonio Recchiuti; Rong Yang; Charles N Serhan
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-01-04
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  121     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-02     Completed Date:  2011-03-28     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  569-81     Citation Subset:  AIM; IM    
Affiliation:
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115-5727, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents, Non-Steroidal / immunology
Arachidonate 5-Lipoxygenase / genetics,  metabolism
Aspirin / immunology
Cyclooxygenase 2 / metabolism
Eicosapentaenoic Acid / analogs & derivatives*,  biosynthesis*,  blood
Fatty Acids, Omega-3 / immunology,  metabolism
Fish Oils / administration & dosage,  chemistry
Humans
Inflammation / immunology*
Leukocytes / immunology*
Mice
Molecular Structure
Recombinant Proteins / genetics,  metabolism
Stereoisomerism
Grant Support
ID/Acronym/Agency:
DK074448/DK/NIDDK NIH HHS; GM38765/GM/NIGMS NIH HHS; R01 GM038765-25/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Fatty Acids, Omega-3; 0/Fish Oils; 0/Recombinant Proteins; 1553-41-9/Eicosapentaenoic Acid; 50-78-2/Aspirin; EC 1.13.11.34/Arachidonate 5-Lipoxygenase; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human
Comments/Corrections

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