Does superoxide radical have a role in macrophage-mediated oxidative modification of LDL?
Low-density lipoprotein (LDL) oxidation induced by superoxide radicals generated in a cell-free system could not stimulate the subsequent development of high-uptake LDL during incubation in a medium normally permissive for cell-mediated oxidation. Similarly, LDL oxidative modification by macrophages was not accelerated when extracellular superoxide generation was increased 5-10-fold by stimulation of NADPH oxidase. The NADPH oxidase inhibitor, diphenylene iodonium, did inhibit macrophage-mediated modification of LDL, but its effects do not appear to involve superoxide generation. Superoxide dismutase (SOD) was shown to be inappropriate as a test for the involvement of superoxide radicals in cell-mediated oxidation due to its metal-chelating properties and to the development of a pro-oxidant activity by heat inactivation. We conclude that there is presently no secure evidence for the involvement of superoxide radical in macrophage-mediated oxidative modification of LDL.
Cell Biology Group, Heart Research Institute, Camperdown, Sydney, N.S.W., Australia.
W
W
Jessup
J A
JA
Simpson
R T
RT
Dean
D000818:Animals; D002474:Cell-Free System; D002478:Cells, Cultured; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D016897:Respiratory Burst; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism / Q000494:pharmacology*
D008077:Lipoproteins, LDL; D013481:Superoxides; D013482:Superoxide Dismutase