ROLE OF OXIDANT INJURY ON MACROPHAGE LIPOPROTEIN-LIPASE (LPL) PRODUCTION AND SENSITIVITY TO LPL

We investigated, in the present study, the role of reactive oxygen int ermediates (ROI) in the control of macrophage lipoprotein lipase (LPL) secretion. Exposure of murine macrophages to increasing concentration s of hydrogen peroxide (H2O2) resulted in enhanced basal LPL productio n and mRNA levels. The increase of LPL production was reduced in the p resence of antioxidants. Oxidant stress also modulated the regulation of macrophage LPL production by tumor necrosis factor alpha (TNF alpha ). While antioxidants accentuated the inhibition of LPL by TNF alpha, addition of H2O2 significantly attenuated TNF alpha-induced LPL inhibi tion. As LPL has been shown to induce macrophage TNF alpha release, th e effect of reactive oxygen species on LPL-induced TNF alpha productio n was also examined. Simultaneous treatment of macrophages with LPL an d H2O2 or pretreatment of macrophages with H2O2 prior to LPL stimulati on decreased the LPL-induced TNF alpha release by macrophages to the s ame extent. Under these experimental conditions, LPL binding to macrop hages was markedly decreased. These data indicate that ROI are effecti ve enhancers of macrophage LPL production and modulate macrophage resp onse to LPL. These effects may represent additional mechanisms through which oxidant stress may participate to the development of atheroscle rosis.-Renier, G., A-C. Desfaits, A. Lambert, and R. Mikhail. Role of oxidant injury on macrophage lipoprotein lipase (LPL) production and s ensitivity to LPL.