Interferon-gamma stimulates lipid metabolism in human monocytes

In nonactivated human monocytes, radiolabeled oleic, arachidonic, and palmitic acids are primarily incorporated into neutral lipids and phosphatidylcholine. Each of these fatty acids is also incorporated into phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and sphingomyelin in characteristic proportions which do not differ between donors. The phospholipid head group precursors, choline and serine, are incorporated into phosphatidylcholine, and phosphatidylserine and serine is incorporated into phosphatidylethanolamine and sphingomyelin. The incorporation of these lipid precursors and the total lipid content of monocytes activated with interferon-gamma were compared to those of nonactivated monocytes. Fatty acid incorporation into interferon-gamma-activated monocytes was dramatically increased, particularly for palmitic acid. Palmitic acid incorporation into phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and sphingomyelin was increased in activated cells by 167-387% at 2 hr and 215-274% at 4 hr compared to that of controls. The greatest increase in incorporation was for palmitic acid into sphingomyelin. Incorporation of arachidonic acid into phosphatidylinositol and serine into phosphatidylethanolamine was also increased in the interferon-gamma-activated monocytes. The total lipid content of activated and nonactivated monocytes did not differ. These results suggest that IFN-gamma activation induces a short-term stimulation of phospholipid metabolism which does not alter the gross lipid composition. Such modifications of phospholipid metabolism may be important in signal transduction as well as an indication of functional changes in the membranes of activated macrophages.