Rapid appearance of resolvin precursors in inflammatory exudates: novel mechanisms in resolution.
Resolution of inflammation is essential. Although supplementation of omega-3 fatty acids is widely used, their availability at sites of inflammation is not known. To this end, a multidisciplinary approach was taken to determine the relationship of circulating omega-3 to inflammatory exudates and the generation of resolution signals. In this study, we monitored resolvin precursors in evolving exudates, which initially paralleled increases in edema and infiltrating neutrophils. We also prepared novel microfluidic chambers to capture neutrophils from a drop of blood within minutes that permitted single-cell monitoring. In these, docosahexaenoic acid-derived resolvin D1 rapidly stopped neutrophil migration, whereas precursor docosahexaenoic acid did not. In second organ injury via ischemia-reperfusion, resolvin metabolically stable analogues were potent organ protectors reducing neutrophils. Together, these results indicate that circulating omega-3 fatty acids rapidly appear in inflammatory sites that require conversion to resolvins that control excessive neutrophil infiltration, protect organs, and foster resolution.
Kasuga
Kie
K
Department of Anesthesiology, Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Boston, MA 02115, USA.
Yang
Rong
R
Porter
Timothy F
TF
Agrawal
Nitin
N
Petasis
Nicos A
NA
Irimia
Daniel
D
Toner
Mehmet
M
Serhan
Charles N
CN
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D001202:Ascitic Fluid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D002464:Cell Migration Inhibition; D015194:Diffusion Chambers, Culture; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D005122:Exudates and Transudates / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010538:Peritonitis / Q000097:blood / Q000276:immunology / Q000473:pathology; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015525:Fatty Acids, Omega-3; D018836:Inflammation Mediators; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid