Modulation of Arachidonic Acid Metabolism in Rat Peritoneal Macrophages Through Nutritional Means

132 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1983.Prostaglandins, synthesized from arachidonic acid (20:4(omega)6) in high amounts by the macrophage, are known to regulate a number of activities important to the immune response. In view of the findings that (alpha)-linolenic acid (18:3(omega)3) inhibits the conversion of linoleic acid (18:2(omega)6) to 20:4(omega)6 and that 18:3(omega)3 and both 20:5(omega)3 and 22:6(omega)3, its elongated, desaturated products, inhibit the conversion of 20:4(omega)6 into prostaglandins (PGs), a study of the effect of nutritionally provided (omega)3 fatty acids on the fatty acid composition, PG synthesis, and function of the macrophage was undertaken.Male Sprague-Dawley weanling rats were fed purified diets containing 10% either corn oil or linseed oil, providing a low (1/32) or high (3.5/1) ratio of 18:3(omega)3 to 18:2(omega)6, respectively. Phospholipid fatty analysis of macrophages from animals fed the diets showed an appreciable increase in the percentage of (omega)3 fatty acids and a decrease in the (omega)6 fatty acids in macrophages from rats fed linseed oil. These changes were associated with a significant decrease in PG synthesis and shown not to involve increased PG degradation.These results were comparable to those found in macrophages cultured with 20:4(omega)6 or 20:5(omega)3. Differences in phospholipid content of 20:4(omega)6 in macrophages altered in vitro were more striking than those in macrophages altered in vivo; however, in both cases, choline phosphoglyceride exhibited the greatest disparity in 20:4(omega)6 content between the two nutritional treatments. Macrophages altered in vitro exhibited marked differences in their ability to synthesize PGE. Those cultured with 20:5(omega)3 synthesized approximately one-tenth the amount synthesized by macrophages cultured with 20:4(omega)6. Culturing with 20:4(omega)6 or 20:5(omega)3 also overcame dietarily induced changes in PG synthesis.Activities of the macrophage reported to be influenced by PGs were examined. Phagocytosis was not altered by the increase in dietary 18:3(omega)3. In agreement with previous reports, arginase activity was greater in macrophages showing greater PG synthesis. The synthesis of H(,2)O(,2) as measured by chemiluminescence was greater in macrophages cultured with 20:5(omega)3 than with 20:4(omega)6; however, since indomethacin, an inhibitor of PG synthesis, did not increase chemiluminescence in the 20:4(omega)6-cultured cells, it was concluded this effect was not mediated by PGs.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD