Lipid mediators protectins

DHA is very abundant in excitable membranes in the retina and brain, particularly in PL of the rod outer segment of retina and of synaptic vesicles, and is important in vision. However, the mechanism by which DHA functions in retina is not well understood. Chen et al. (Y. Chen, 1993) suggest that DHA in retina might be involved in shuttling 11-c/j-retinal to photoreceptors, whereas Niu et al. (S. Niu, 2004) propose that DHA in PL increases the efficiency of G-protein-mediated signal transduction of rhodopsin. In humans, supplementation of infant formula with DHA accelerates the development of visual functions in pre-term infants. The novel protective lipid mediator docosanoids, namely, Protectin D1 (C. Serhan, 2002) and 17S-hydroperoxy-DHA (V. Marcheselli, 2003), have been suggested to mediate the beneficial effects of DHA. 

This chapter summarizes recent findings involving the formation and biological roles of several new types of polyunsaturated anti-inflammatory and pro-resolving lipid mediators [1], such as lipoxins, resolvins, protectins, and maresins (MaR). These molecules are able to dampen the inflammatory response, promote the resolution of inflammation, and exhibit other beneficial actions at inflammatory sites [2-4]. 

DHA, a C22 6 omega-3 (co-3) fatty acid, is a major lipid component in the brain and eye [14], and a common ingredient of fish oil. DHA is an extensively stndied PUFA, and its enzymatic oxygenation leads to several series of benehcial lipid mediators (docosanoids), including D-resolvins (RvD) [15], protectins/nenroprotectins (PD/NPD) [16-19], and maresins (MaR) [20-22]. 

This chapter is focused on the biosynthesis and actions of lipoxins, resolvins, protectins, and maresins. Each group of PUFA-derived lipid mediators has its own distinct biosynthetic pathways and features a specialized biological activity profile. 

A large number of studies on the biological actions of the lipoxins and their stable analogs revealed the multi-faceted biological roles of this class of lipid mediators [8,10,11,27,28,30,31,35,37-63], Selected examples of applications in various disease models are summarized in the section Beneficial Roles of Lipoxins, Resolvins, Protectins, and Maresins (Table 9.1). 

The complete R/S and Z/E stereochemistry of this docosanoid was established by direct comparison and matching of its chemical and biological properties using several synthetic stereochemically pure stereoisomers [18]. The synthetic materials were also used to investigate in detail the anti-inflammatory properties and other actions of this lipid mediator, which was also termed protectin D1 (PDl) to indicate its broader scope [18]. 

The lipid mediators derived from ARA, EPA, and DHA discussed above (i.e., lipox-ins, resolvins, protectins, and maresins) have different biosynthetic origins and variable overall bioactivity profiles. These molecules have been collectively termed specialized pro-resolving lipid mediators (SPM), due to their conunon biological role, namely their ability to reduce the inflanunatory response, and to promote the resolution of inflammation and return to homeostasis. 

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