MACROPHAGE ACTIVATION BY LIPOPOLYSACCHARIDE, INTERFERON-GAMMA AND INTERLEUKIN-4 - EFFECT OF FATTY-ACID METABOLISM

THE aim of this study was to investigate the effects of interferon-gamma and -beta (IFN-gamma, -beta), interleukin-4 and -10 (IL-4, -10) and lipopolysaccharide (LPS) on the metabolism and composition of phospholipid fatty acids in macrophages. Murine J774.2 macrophages were incubated with radiolabelled fatty acids and the appropriate stimulus and the incorporation and composition of the phospholipid classes was determined. IFN-gamma and IL-4 specifically stimulated enhanced incorporation of [C-14]-linoleic acid into the phosphatidylethanolamine fraction. IL-4 (in contrast to IFN-gamma and LPS) reduced incorporation of [C-14]arachidonic acid into phosphatidylinositol Incubation of J774.2 cells with linoleic acid significantly increased TNF alpha and nitric oxide production; arachidonic acid enhanced TNF alpha production but reduced nitric oxide production. It is concluded that lFN-gamma, IL-4 and IL-10 may differentially regulate macrophage activation via effects on the metabolism of polyunsaturated fatty acids.