Resolvin E2 Formation and Impact in Inflammation Resolution

Abstract

Acute inflammation and its resolution are essential processes for tissue protection and homeostasis. In this context, specialized proresolving mediators derived from polyunsaturated fatty acids are of interest. In this study, we report that resolvin E2 (RvE2) from eicosapentaenoic acid is endogenously produced during self-limited murine peritonitis in both the initiation and resolution phases. RvE2 (1–10 nM) carries potent leukocyte-directed actions that include: 1) regulating chemotaxis of human neutrophils; and 2) enhancing phagocytosis and anti-inflammatory cytokine production. These actions appear to be mediated by leukocyte G-protein–coupled receptors as preparation of labeled RvE2 gave direct evidence for specific binding of radiolabeled RvE2 to neutrophils (Kd 24.7 ± 10.1 nM) and resolvin E1 activation of recombinant G-protein–coupled receptors was assessed. In addition to the murine inflammatory milieu, RvE2 was also identified in plasma from healthy human subjects. RvE2 rapidly downregulated surface expression of human leukocyte integrins in whole blood and dampened responses to platelet-activating factor. Together, these results indicate that RvE2 can stimulate host-protective actions throughout initiation and resolution in the innate inflammatory responses.

Computational Approach To Characterize Causative Factors and Molecular Indicators of Chronic Wound Inflammation

“…Moreover, we do not explicitly define tissue-specific cells, such as resident macrophages, mast cells, and connective tissue cells. Our model is based on the notion that key participants (neutrophils and macrophages) and interactions in the local inflammatory process may be sufficiently similar across many, or most, inflammatory situations (3,11,14,16,52,57,77,78). Therefore, although we modeled chronic inflammation in (traumatic) wounds, we expect that our findings may be applicable in other contexts, which is supported by comparisons of our modeling results with experimental studies of noninjury-induced inflammation (Figs.…”

Specific lipid mediator signatures of human phagocytes: microparticles stimulate macrophage efferocytosis and pro-resolving mediators

“…7 SPM biosynthesis, including RvE2, peaks during the resolution phase with levels for this mediator reaching ϳ 2.5 pg/ mouse exudate. 34 Similarly, in murine models of live infections, PGE 2 levels peak with the onset of resolution, reaching ϳ 1773 pg/ mouse exudate. 35 Hence, the present findings with isolated human PMN staged in vitro (ie, on activation, progression to apoptosis, and during macrophage efferocytosis) follow the in vivo events and levels of LM in self-contained exudates.…”

The role of 15-LOX-1 in colitis and colitis-associated colorectal cancer

“…The mice also exhibited less weight loss, reduced overall mortality, and no significant shortening or thickening of the colon [63], all of which are important in diminishing colitis [63,67]. RvE1 and RvE2 have a direct interaction with PMN migration, suggesting that these resolvins have anti-inflammatory and inflammation-resolving properties [68]. RvE1 and RvE2 both significantly reduce zymosan-induced PMN infiltration [24,69].…”

“…RvE1 and RvE2 both significantly reduce zymosan-induced PMN infiltration [24,69]. RvE2 demonstrates nonphlogistic leukocyte action by increasing the secretion of IL-10 dose dependently in human macrophages [68]. RvE1 fuels increased clearance of invading microbes, other cellular debris [24], and live bacteria [70].…”