GLUTATHIONE-PEROXIDASE ACTIVITY AND METABOLISM OF ARACHIDONIC-ACID IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM ELDERLY SUBJECTS

1. Since ageing has been associated with a decrease in both immune responses and antioxidant defences, this study was undertaken to compare the glutathione peroxidase activity in peripheral blood mononuclear cells of healthy elderly and young donors. The mean value of glutathione peroxidase activity was significantly lower in the aged group (-36%) than that observed in the young control group n=10). 2. This defect was accompanied by a marked increase (+106%) in the oxygenated metabolism of endogenous arachidonic acid by lipoxygenases as judged by the radiolabel associated with hydroxyeicosatetraenoic acids in [H-3]arachidonic acid-prelabelled peripheral blood mononuclear cells, whereas the cyclo-oxygenase activity, estimated by the radiolabel associated with thromboxane B2, was not significantly altered. 3. Upon stimulation by the mitogenic lectin concanavalin A, the radioactivity associated with total eicosanoids (free arachidonic acid plus hydroxyeicosatetraenoic acids plus thromboxane B2) was significantly increased over basal levels in the peripheral blood mononuclear cells of both the elderly and the control groups. However, the mitogen-induced increase was lower in the elderly group (+48%) than in the control group (+131%). Upon concanavalin A stimulation, the radioactivity of hydroxyeicosatetraenoic acids was increased by only 96% in peripheral blood mononuclear cells from the elderly group compared with 350% in control cells. Similarly, the radioactivity associated with thromboxane B2 was increased by only 82% in peripheral blood mononuclear cells from the elderly group compared with 218% in control cells. 4. Reverse phase h.p.l.c. of the hydroxyeicosatetraenoic acids showed that, in unstimulated peripheral blood mononuclear cells, the 12-hydroxyeicosatetraenoic acid level tended to be higher in the elderly group than in the control group, which might be indicative of an hyperactivity of the contaminating platelets in peripheral blood mononuclear cells from elderly subjects. However, in stimulated cells, the concanavalin A-induced increase in 12-hydroxyeicosatetraenoic acid proved to be lower in the elderly group (+283%) than in the control group (+814%). 5. Furthermore, the concanavalin A-induced release of arachidonic acid from the phosphoinositide pool was also decreased in the elderly group as compared with the control group. These results suggest that the major defect of arachidonic acid metabolism in peripheral blood mononuclear cells from elderly subjects might be located at the level of its mitogen-induced liberation known to occur during the early steps of lymphocyte activation. An eventual implication of the lowered glutathione peroxidase activity in the observed abnormalities of arachidonic acid metabolism in cells from aged subjects is discussed.