Alteration of platelet-activating factor-induced signal transduction in macrophages by n-3 fatty acids

Diets rich in polyunsaturated n-3 fatty acids can alter various macrophage functions. One possible mechanism by which this occurs is through modulation of the physicochemical properties of the cell membrane and the signal transduction pathways associated with macrophage activation. In this study, we investigated how n-3 fatty acids altered the signaling pathway of the lipid-based mediator platelet-activating factor (PAF). Macrophages from mice fed a diet containing n-3 fatty acids showed a greater increase in PAF-induced intracellular Ca2+ mobilization than macrophages from mice fed an n-6 fatty acid-rich diet. Macrophages treated in vitro with the n-3 fatty acids docosahexaenoic and eicosapentaenoic also showed higher intracellular Ca2+ mobilization than untreated or n-6 fatty acid-treated macrophages. Scatchard analysis of PAF binding showed the presence of one type of PAF receptor; their number and affinities were not altered by dietary fat. Mastoparan, which can activate G-protein-linked phosphoinositide (PI)-signaling pathway through the activation of G proteins, stimulated a higher Ca2+ mobilization in macrophages from mice fed n-3 compared to n-6 fatty acids. In addition, the response of macrophages from n-3-fed mice to PAF was less sensitive to phospholipase C inhibition than that of macrophages from those fed n-6 diets. The activity of phospholipase C in macrophages from mice fed n-3 diets was significantly higher than that of macrophages from mice fed diets containing n-6 fatty acids. Collectively, these results showed that n-3 fatty acids can enhance the PAF-signaling pathway in macrophages by increasing the activation potential of phospholipase C, without affecting PAF receptor number and affinity.