Glomerular macrophages in nephrotoxic serum nephritis are activated to oxidize low-density lipoprotein.
Studies were undertaken to investigate the hypothesis that infiltrating glomerular macrophages in experimental glomerulonephritis are activated to produce oxygen-free radicals that are capable of enhancing oxidation of low-density lipoprotein (LDL). Low-density lipoprotein oxidation was assessed by increased electrophoretic mobility on agarose gel electrophoresis and by the generation of thiobarbituric acid-reactive substances. Lipoprotein uptake, degradation, and re-esterification by macrophages were assessed by measuring 14C-oleic acid incorporation into cholesteryl oleate. Both peritoneal and glomerular macrophages have the ability to oxidize LDL to a form showing increased mobility on agarose gel electrophoresis. However, LDL incubated with glomerular macrophages underwent greater oxidation, resulting in increased generation of thiobarbituric acid-reactive substances (15.1 +/- 1.2 nmol malondialdehyde/mg LDL protein v 7.2 +/- 2.1 nmol malondialdehyde/mg LDL protein; P < 0.01). In addition, glomerular macrophages modified LDL to a form that greatly enhanced cellular synthesis of cholesteryl oleate compared with peritoneal macrophage-modified LDL (30 +/- 11 pmol/10(6) cells/hr v 10 +/- 4 pmol/10(6) cells/hr; P < 0.01). Superoxide dismutase, a scavenger of superoxide anion, inhibited macrophage-mediated oxidation of LDL. These results suggest that glomerular macrophages from nephritic rats are activated to modify LDL to a form avidly taken up by macrophage scavenger receptors. Thus, enhanced formation of oxidized LDL by infiltrating glomerular macrophages may contribute to glomerular injury in nephrotoxic serum nephritis.
Rie
J
J
Department of Medicine, Montefiore Medical Center, Bronx, NY, USA.
Silbiger
S
S
Neugarten
J
J
D000818:Animals; D002788:Cholesterol Esters / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D009829:Oleic Acids; D017392:Thiobarbituric Acid Reactive Substances; D019301:Oleic Acid; C014409:cholesteryl oleate