Resolvin D1 binds human phagocytes with evidence for proresolving receptors

By S. Krishnamoorthy, A. Recchiuti, Chia Nan, S. Yacoubian, Chih‐Hao Lee, Rong Yang, N. Petasis, C. Serhan. Proceedings of the National Academy of Sciences of the United States of America, 2010

753 citations recorded by the source corpus.

Endogenous mechanisms that act in the resolution of acute inflammation are essential for host defense and the return to homeostasis. Resolvin D1 (RvD1), biosynthesized during resolution, displays potent and stereoselective anti-inflammatory actions, such as limiting neutrophil infiltration and proresolving actions. Here, we demonstrate that RvD1 actions on human polymorphonuclear leukocytes (PMNs) are pertussis toxin sensitive, decrease actin polymerization, and block LTB4-regulated adhesion molecules (β2 integrins). Synthetic [3H]-RvD1 was prepared, which revealed specific RvD1 recognition sites on human leukocytes. Screening systems to identify receptors for RvD1 gave two candidates—ALX, a lipoxin A4 receptor, and GPR32, an orphan—that were confirmed using a β-arrestin-based ligand receptor system. Nuclear receptors including retinoid X receptor-α and peroxisome proliferator-activated receptor-α, -δ, -γ were not activated by either resolvin E1 or RvD1 at bioactive nanomolar concentrations. RvD1 enhanced macrophage phagocytosis of zymosan and apoptotic PMNs, which increased with overexpression of human ALX and GPR32 and decreased with selective knockdown of these G-protein-coupled receptors. Also, ALX and GPR32 surface expression in human monocytes was up-regulated by zymosan and granulocyte-monocyte–colony-stimulating factor. These results indicate that RvD1 specifically interacts with both ALX and GPR32 on phagocytes and suggest that each plays a role in resolving acute inflammation.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0a63adcab899eb09be1892c9ad2fcf99bcdff55d

How researchers see this paper

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

In Immunology

In Molecular Biology

Citations in the corpus

Anti-inflammatory Agents: Present and Future (2010, positive): “Specific receptors for resolvins have been identified and when activated are functional in reducing inflammation (Krishnamoorthy et al., 2010).”
Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs. (2015, background): “Resolvins have been shown to have protective actions in inflammatory diseases (97, 391, 392), whereas the effects of protectins vary by isomer—protectin DX has antiaggregatory effects (326, 393) and can restore insulin sensitivity in obese mice (329), but protectin D1 does not exhibit these activiti”
Discovery of Human Signaling Systems: Pairing Peptides to G Protein-Coupled Receptors (2019, background): “In contrast, we found no activity for other proposed peptide/GPCR pairings such as adropin/GPR19 (Stein et al., 2016), head activator/GPR37 (Rezgaoui et al., 2006), prosaptide/GPR37/GPR37L1 (Meyer et al., 2013; Rezgaoui et al., 2006), and galanin/GPR151 (Ignatov et al., 2004) or for the lipid/GPCR p”
Specialized pro-resolving mediators: endogenous regulators of infection and inflammation (2015, background): “In addition to RvD1, AT-RvD1 and RvD3 bind to GPR32 with high affinity [49] [50] [51] .”