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-gam ma and -beta (IFN-gamma, -beta), interleukin-4 and -10 (IL-4, -10) and lipopolysaccharide (LPS) on the metabolism and composition of phospho lipid fatty acids in macrophages. Murine J774.2 macrophages were incub ated with radiolabelled fatty acids and the appropriate stimulus and t he incorporation and composition of the phospholipid classes was deter mined. IFN-gamma and IL-4 specifically stimulated enhanced incorporati on of [C-14]-linoleic acid into the phosphatidylethanolamine fraction. IL-4 (in contrast to IFN-gamma and LPS) reduced incorporation of [C-1 4]arachidonic acid into phosphatidylinositol Incubation of J774.2 cell s with linoleic acid significantly increased TNF alpha and nitric oxid e production; arachidonic acid enhanced TNF alpha production but reduc ed nitric oxide production. It is concluded that lFN-gamma, IL-4 and I L-10 may differentially regulate macrophage activation via effects on the metabolism of polyunsaturated fatty acids.