Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis

By Matthew Spite, L. Norling, L. Summers, Rong Yang, D. Cooper, N. Petasis, R. Flower, M. Perretti, C. Serhan. Nature, 2009

711 citations recorded by the source corpus.

A growing body of evidence indicates that resolution of acute inflammation is an active process. Resolvins are a new family of lipid mediators enzymatically generated within resolution networks that possess unique and specific functions to orchestrate catabasis, the phase in which disease declines. Resolvin D2 (RvD2) was originally identified in resolving exudates, yet its individual contribution in resolution remained to be elucidated. Here, we establish RvD2’s potent stereoselective actions in reducing excessive neutrophil trafficking to inflammatory loci. RvD2 decreased leukocyte–endothelial interactions in vivo by endothelial-dependent nitric oxide production, and by direct modulation of leukocyte adhesion receptor expression. In mice with microbial sepsis initiated by caecal ligation and puncture, RvD2 sharply decreased both local and systemic bacterial burden, excessive cytokine production and neutrophil recruitment, while increasing peritoneal mononuclear cells and macrophage phagocytosis. These multi-level pro-resolving actions of RvD2 translate to increased survival from sepsis induced by caecal ligation and puncture and surgery. Together, these results identify RvD2 as a potent endogenous regulator of excessive inflammatory responses that acts via multiple cellular targets to stimulate resolution and preserve immune vigilance.

Subfields: Biochemistry, Immunology, Nutrition and Dietetics

View Paper: https://www.semanticscholar.org/paper/e43795d32b462521d1fb2f1ece009104876da993

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biochemistry

1. B. Levy
2. M. Basil
3. Oliver Soehnlein
4. N. Borregaard
5. C. Serhan
6. L. Lindbom
7. P. Calder
8. T. Kern

In Immunology

1. P. Kubes
2. Oliver Soehnlein
3. A. Mantovani
4. B. Levy
5. C. Serhan
6. S. Jaillon
7. N. Borregaard
8. Rongbin Zhou

In Nutrition and Dietetics

1. B. Levy
2. M. Basil
3. N. Borregaard
4. Oliver Soehnlein
5. L. Lindbom
6. J. Tschopp
7. C. Serhan
8. P. Calder

Citations in the corpus

• Specialized pro-resolving mediators: endogenous regulators of infection and inflammation (2015, background): “Recent discoveries [11] [12] [13] [14] [15] regarding anti-inflammatory, anti-infective and proresolving roles for SPMs point to their potential translational applications in harnessing endogenous resolution responses for novel host-directed therapeutic strategies in sterile and infectious inflammat”
• Interactions between the immune and nervous systems in pain (2010, background): “Resolvin D1 (RvD1) inhibits IL-1β production in microglia, and RvD2 attenuates neutrophil migration to the site of inflammation by inhibiting leukocyte-endothelial interactions in vivo”
• The neutrophil in vascular inflammation (2011, background): “Most studies have focused on how neutrophil recruitment at this stage r e v i e w is turned off, with molecules such as resolvins taking center stage 72 .”
• Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs. (2015, neutral): “LOX oxylipins 14,20-DiHDoHE Inhibits PMN infiltration in the mouse peritonitis model (101) 14,21-DiHDoHE Enhances wound healing in murine models (313, 314) 4-HDoHE Inhibits endothelial cell proliferation and sprouting angiogenesis in mouse model of oxygen-induced retinopathy (315) 7-HDoHE Activates ”
• Neutrophils, from marrow to microbes. (2010, background): “Resolvin D2 has recently been shown to inhibit neutrophil activation and to augment the generation of nitric oxide by endothelial cells (Spite et al., 2009).”
• Phagocyte partnership during the onset and resolution of inflammation (2010, background): “In a complementary approach, it has repeatedly been shown that pro-resolving lipid mediators such as lipoxins, resolvins, protectins and maresins promote the return to tissue homeostasi”
• Neutrophils in the activation and regulation of innate and adaptive immunity (2011, background): “These pro-resolving lipid mediators and the recently described macrophage-derived compound maresin 1 inhibit neutrophil transendothelial migration and tissue infiltratio”
• Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines (2018, background): “In normal inflammation SPMs do not compromise host immune competence with examples of pro-resolving mediators increasing survival from infections in mouse models (28, 29).”
• Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. (2018, background): “RvD2 also carries potent organ-protective actions and enhances bacterial killing/clearance (53).”