Biosynthesis of DPAn-3-derived 13-series resolvins

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Homo sapiens
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Neutrophils adherence to the vascular endothelium is a critical and early event in the innate immune response to injury or invading pathogens (Sadik et al. 2011). Studies of the lipid fraction from neutrophil-endothelial cell cultures resulted in the discovery of four novel specialised proresolving mediators (SPMs) (Dalli et al. 2015). Results from LC/MS-MS metabololipidomics using a chemically-synthesised precursor (13(R)-hydroxy-DPAn-3) identified four mediators generated from this precursor.

The polyunsaturated fatty acid (PUFA) ω-3 cis-7,10,13,16,19-docosapentaenoic acid (DPAn-3) is an intermediate in the biosynthesis of docosahexaenoic acid (DHA) from eicosapentaenoic acid (EPA) and is also a precursor for the production of novel bioactive mediators. DPAn-3 can form this precursor when acted upon by cyclooxygenase 2 (COX2). Thus these novel 13-series resolvins (RvT1-4) originate from DPAn-3 (Primdahl et al. 2016). In E. coli-infected mice, RvTs accelerated resolution of inflammation and increased survival. RvTs also regulated human and mouse phagocyte responses, stimulating bacterial phagocytosis and regulating inflammasome components (Dalli et al. 2015). The biosynthetic routes of these RvTs are described here. RvT formation requires neutrophil-endothelial cell interaction and is thought to proceed via a two-step process; COX2 hydroxylates DPAn-3 to 13(R)-DPAn-3 which trafficks to adjacent neutrophils where it is lipoxygenated by 5-lipoxygenase to RvT1-4 (Vik et al. 2017).

Literature References
PubMed ID Title Journal Year
28408222 Recent advances in the chemistry and biology of anti-inflammatory and specialized pro-resolving mediators biosynthesized from n-3 docosapentaenoic acid

Vik, A, Dalli, J, Hansen, TV

Bioorg. Med. Chem. Lett. 2017
26236990 Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections

Dalli, J, Chiang, N, Serhan, CN

Nat. Med. 2015
27704804 Synthesis of 13(R)-Hydroxy-7Z,10Z,13R,14E,16Z,19Z Docosapentaenoic Acid (13R-HDPA) and Its Biosynthetic Conversion to the 13-Series Resolvins

Primdahl, KG, Aursnes, M, Walker, ME, Colas, RA, Serhan, CN, Dalli, J, Hansen, TV, Vik, A

J. Nat. Prod. 2016
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