page 713, Arita et al. decipher the structure of an antiinflammatory lipid in humans that is derived from an essential fatty acid in fish oil.
Fatty fish contain large amounts of omega-3 fatty acids—diet-derived essential fatty acids known to benefit patients with cardiovascular disease and arthritis. This group recently identified a new class of aspirin-triggered bioactive lipids, called resolvins, the activity of which may in part explain the beneficial effects of omega-3 fatty acids. Resolvins are synthesized from the omega-3 fatty acids by cellular enzymes and are potent counterregulators of inflammation in mice. The main bioactive component of this class of lipids was identified in mice and named resolvin E1.
Recent clinical trials showing that omega-3 fatty acids combined with aspirin reduced the risk of heart attack prompted the authors to look for resolvin E1 in humans. They have now identified this lipid in plasma taken from volunteers given omega-3 fatty acids and aspirin, deciphered its complete stereochemical structure, and identified its receptor.
Human resolvin E1, the authors show, binds to a G protein–coupled receptor called ChemR23 that is expressed on leukocytes, and inhibits the migration of these cells to sites of inflammation. Resolvin E1 might also affect adaptive immunity in response to pathogens, as it reduced the production of interleukin-12 by dendritic cells and inhibited their migration to T cell areas of the spleen in mice.In previous studies, aspirin promoted the cyclooxygenase-2 (COX-2)–dependent conversion of omega-3 fatty acids to a precursor of resolvin E1. COX-2 also converts arachidonic acid, another essential fatty acid, into proinflammatory prostaglandins. COX-2 inhibitors, designed to block this proinflammatory pathway, have had negative cardiovascular side effects. The authors thus suggest that inhibition of vascular COX-2 might also block the synthesis of resolvin E1, which would eliminate an important antiinflammatory pathway.