Lipid mediator class switching during acute inflammation: signals in resolution

BD Levy, CB Clish, B Schmidt, K Gronert… - Nature …, 2001 - nature.com
BD Levy, CB Clish, B Schmidt, K Gronert, CN Serhan
Nature immunology, 2001nature.com
Abstract 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 PGE 2 (as in exudates) switched eicosanoid biosynthesis from …
Abstract
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 PGE 2 (as in exudates) switched eicosanoid biosynthesis from predominantly LTB 4 and 5-lipoxygenase (5-LO)–initiated pathways to LXA 4, 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.
nature.com