Resolvin D3 multi-level proresolving actions are host protective during infection.

Area of Science:

• Immunology
• Infectious Diseases
• Biochemistry

Background:

• Innate immune cells govern infection and inflammation resolution.
• Resolvins, a class of n-3 mediators, promote neutrophil clearance and reduce pro-inflammatory signals.
• Endogenous resolvin D3 (RvD3) was identified in self-resolving exudates during active E. coli infection.

Purpose of the Study:

• To synthesize RvD3 and evaluate its immunoresolvent actions in E. coli peritonitis.
• To investigate RvD3's effects on leukocyte phagocytosis, pro-inflammatory mediators, and platelet-PMN aggregation.

Main Methods:

• Metabololipidomics to identify endogenous RvD3.
• Independent synthetic route for RvD3 production and characterization.
• In vivo administration of RvD3 during E. coli peritonitis in a mouse model.
• In vitro assays assessing RvD3's effects on human macrophages and neutrophils.

Main Results:

• Synthetic RvD3 matched endogenous RvD3.
• RvD3 significantly reduced the resolution interval (approx. 4.5 hours) during E. coli peritonitis.
• RvD3 enhanced phagocytosis of E. coli and neutrophils, reduced pro-inflammatory cytokines, chemokines, MMP-2, and MMP-9.
• RvD3 increased human macrophage and neutrophil phagocytosis, enhanced neutrophil ROS generation, and reduced platelet-PMN aggregation at pM-nM concentrations.

Conclusions:

• RvD3 exhibits potent immunoresolvent properties, accelerating infection resolution.
• RvD3 enhances host defense and protection against bacterial infection.
• RvD3 demonstrates significant antimicrobial defense capabilities.