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Chapter 17 : Novel Anti-Inflammatory and Proresolution Lipid Mediators in Induction and Modulation of Phagocyte Function
Category: Microbial Genetics and Molecular Biology; Bacterial Pathogenesis
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Several novel enzymatic pathways were recently identified that are activated during the resolution phase and initiated from precursors eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The protectin family name signifies their formation, potent anti-inflammatory, as well as protective actions demonstrated for the novel and potent DHA-derived 10,17-docasatriene in animal models of stroke and Alzheimer’s disease. Both families, the resolvins and protectins, are potent local-acting agonists of endogenous anti-inflammation and promote resolution-specific processes. The connection(s) of these new lipid mediators to the control of an acute inflammation and its timely resolution are illustrated in this chapter. The chapter focuses on biosynthesis of proresolving mediators via cyclooxygenases and lipoxygenases. COX-2 also plays a key role in the biosynthesis of PGD2, which is a precursor to the cyclopentenones. Precursors are transformed via enzymatic mechanisms to bioactive compounds such as lipoxins, resolvins, and protectins that regulate the duration and magnitude of inflammation. The most likely human cell types and pathways that biosynthesize the bioactive mediators within the resolving exudates were reconstructed in vitro, which involved cell-cell interactions in vivo within the exudates. Emerging evidence indicates that the immunomodulatory actions of several lipid mediators are exploited by pathogens, including fungi and helminths. In such cases, it seems that modulation of immunity by suppressing host proinflammatory responses is the aim. The interplay between these mediators, the induction of 5-LO, and the control of immune responses in vivo await further investigation.
Lipid mediators during the initiation and resolution of acute inflammation.
Eicosanoids and their proinflammatory and proresolution actions.
Biosynthesis of E-series resolvins.
Biosynthesis of D-series resolvins.
Protectin D1/neuro-protectin D1 biosynthesis and related dihydroxydocosatrienes.
Leukocyte- and pathogen-mediated synthesis of lipoxins.
Lipoxins reduce inflammation and promote resolution
Lipoxin deficiencies in human disease and proresolving actions after lipoxin analog treatment in animal disease models
Resolvins in models of human diseases
Protectins in models of human diseases