Lipid mediator class switching during acute inflammation: signals in resolution.
Leukotrienes (LTs) and prostaglandins (PGs) amplify acute inflammation, whereas lipoxins (LXs) have unique anti-inflammatory actions. Temporal analyses of these eicosanoids in clinical and experimental exudates showed early coordinate appearance of LT and PG with polymorphonuclear neutrophil (PMN) recruitment. This was followed by LX biosynthesis, which was concurrent with spontaneous resolution. Human peripheral blood PMNs exposed to PGE2 (as in exudates) switched eicosanoid biosynthesis from predominantly LTB4 and 5-lipoxygenase (5-LO)-initiated pathways to LXA4, a 15-LO product that "stopped" PMN infiltration. These results indicate that first-phase eicosanoids promote a shift to anti-inflammatory lipids: functionally distinct lipid-mediator profiles switch during acute exudate formation to "reprogram" the exudate PMNs to promote resolution.
Levy
B D
BD
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Clish
C B
CB
Schmidt
B
B
Gronert
K
K
Serhan
C N
CN
D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics; D001483:Base Sequence; D018076:DNA, Complementary; D015232:Dinoprostone / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D007975:Leukotriene B4 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000276:immunology; D044045:Lipoxins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010996:Pleural Effusion / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
D018076:DNA, Complementary; D006893:Hydroxyeicosatetraenoic Acids; D008055:Lipids; D044045:Lipoxins; D012333:RNA, Messenger; C040527:lipoxin A4; D007975:Leukotriene B4; D001093:Arachidonate 15-Lipoxygenase; D015232:Dinoprostone