Interferon-gamma-stimulated uptake and turnover of linoleate and arachidonate in macrophages: a possible pathway for hypersensitivity to endotoxin.

When P388D macrophage cells were exposed to [14C]linoleic acid, phosphatidylcholine (PC) phosphatidylethanolamine (PE), phosphatidylinositol (PI), and triacylglycerol (TAG) were major labelled lipid classes. PC was the major labelled phospholipid class at shorter incubation times with PE and PI becoming proportionally better labelled with time. Interferon-gamma (IFN-gamma) stimulated the labelling of all phospholipid classes at the expense of triacylglycerol (TAG) labelling whether it was added coincidently to the [14C]linoleic acid or after a prelabelling period. A similar pattern of labelling of all major phospholipid classes by interferon-gamma in J774.2 macrophage cells was also observed. Interferon-gamma also exerted a stimulatory effect on incorporation of [14C]arachidonic acid into the phosphatidylinositol fraction of the membrane phospholipids. However, uptake of [14C]stearic acid was not different in control compared with IFN-gamma-activated cells. Uptake of linoleic acid into the plasmalogen fraction of PE was also considerably enhanced in IFN-gamma-treated cells. The results suggest that IFN-gamma has a direct effect on the activity of enzymes controlling fatty acid turnover in phospholipids. This altered uptake and turnover of unsaturated fatty acids may have important consequences for the subsequent activation of macrophages by endotoxin.