Maresin 1 biosynthesis during platelet–neutrophil interactions is organ-protective

Abstract

Significance Neutrophil accumulation is fundamental to acute inflammation. In response to tissue injury, circulating neutrophil–platelet aggregates (N-PAs) form for secondary capture. Counterregulation of acute inflammatory processes by specialized proresolving mediators is essential to mitigate collateral injury to healthy bystander tissue. Here, we identified a biosynthetic route in human platelets for the proresolving mediator maresin 1 (MaR1) that is amplified during platelet–neutrophil interactions. In a self-resolving murine model of acute lung injury, N-PAs rapidly formed and a MaR1 counterregulatory circuit was engaged to restrain N-PAs and acute inflammation and restore homeostasis of the injured lung.

Protectin D1 n-3 DPA and resolvin D5 n-3 DPA are effectors of intestinal protection

“…Moreover, the relapsing and remitting nature of IBD together with the spontaneous resolution that sometimes is observed (20), suggest existence of contrasting endogenous processes enacted by proinflammatory and proresolving mediators during the pathogenesis of the disease. SPM are produced by leukocytes, including neutrophils and macrophages, via transcellular biosynthesis and in a cellautonomous manner (21,22). Other cell types, including epithelial cells (23) and platelets (21), may also contribute to the SPM production because they carry some of the initiating enzymes in the biosynthesis of these molecules.…”

“…SPM are produced by leukocytes, including neutrophils and macrophages, via transcellular biosynthesis and in a cellautonomous manner (21,22). Other cell types, including epithelial cells (23) and platelets (21), may also contribute to the SPM production because they carry some of the initiating enzymes in the biosynthesis of these molecules. Many of these cell types, including macrophages and epithelial cells, are present in human naïve (healthy) colon biopsies and their numbers are increased in IBD (24).…”

Annexin A1–containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair

“…Recent studies have identified a number of mediators that play an active role in the resolution of inflammation, including ANXA1, lipoxins, resolvins, protectins, and maresins (3,(34)(35)(36)(37). ANXA1 is expressed by a number of cell types, including epithelial cells and phagocytes, and mediates its biological responses by activating FPRs that are expressed in both phagocytes and epithelial cells.…”

Maresin-1 reduces airway inflammation associated with acute and repetitive exposures to organic dust

“…Yet, no previous studies have reported a role for SPM in organic dust-induced inflammation or identified the specific effects that MaR1 may influence during these lung inflammatory processes. MaR1 is has been shown to be produced by neutrophil-platelet aggregates particularly during early stages of an inflammatory response, as well as by macrophages that are activated at sites of inflammation (28, 30). Neutrophil influx is a key marker of DE-induced airway and inflammation, and we have shown macrophages to be important during the resolution of organic dust-mediated effects (39).…”

“…In the case of the SPM maresin-1 (MaR1), reduced neutrophil infiltration and increased macrophage phagocytic capacities were demonstrated in a murine peritonitis model, and pulmonary edema, neutrophil influx, and pro-inflammatory mediator production were reduced in MaR1-treated mice in a lipopolysaccharide-induced acute lung injury model (28,29). In a murine model of acute lung injury, MaR1 was found to decrease lung neutrophils, edema, and pro-inflammatory mediators (30). Furthermore, we found that MaR1 is effective in reducing pro-inflammatory responses associated with organic dust exposures in vitro .…”