Differential effects of arachidonic and eicosapentaenoic Acid-derived eicosanoids on polymorphonuclear transmigration...

The beneficial effects of fish oil on inflammation have been attributed to the content of eicosapentaenoic (EPA)/docosahexaenoic acid. EPA is also a substrate for arachidonic acid (AA) cascade enzymes, but it induces the production of alternative eicosanoids such as 3-series prostanoids and 5-series leukotrienes, which are considered to be less proinflammatory than AA metabolites. However, the molecular basis of this action is poorly understood. In this study, we compared the effects of prostaglandin (PG) E(2) and PGE(3) on endothelium permeability, and the effects of leukotriene (LT) B(4) and LTB(5) on endothelium permeability and mononuclear adhesion and migration. In our study, both prostaglandins increased trans-endothelial Evans blue-albumin (EBA) permeability in a concentration-dependent manner. It is interesting that the effect of PGE(3) was significantly more pronounced than the effect of PGE(2), and both were antagonized by EP(1) and EP(2) antagonists. LTB(4) and LTB(5) had a slight effect on EBA extravasation. However, we observed the enhancement of endothelial permeability in the presence of polymorphonuclear (PMN) cells, probably a consequence of an interplay between leukotriene and prostanoid effects. LTB(4) caused significant increases in the number of PMN cells adhering to endothelial cells, whereas LTB(5) did not induce a significant effect. This effect of LTB(4) appears BLT1 receptor-dependent and was mediated through the enhancement of lymphocyte function-associated antigen-1, membrane attack complex-1, E-selectin, and intercellular adhesion molecule-1 expression. Finally, we observed that, unlike LTB(5), which had a weak effect, LTB(4) was a highly potent chemoattractant. An understanding of the differences in the effects of LTB(4)/LTB(5) on PMN cell adhesion and migration may help to explain the beneficial impact of omega-3 fatty acids in inflammatory processes.