TY - JOUR
T1 - Glomerular macrophages in nephrotoxic serum nephritis are activated to oxidize low-density lipoprotein
AU - Rie, Jonathan
AU - Silbiger, Sharon
AU - Neugarten, Joel
PY - 1995/8
Y1 - 1995/8
N2 - 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/106 cells/hr v 10 ± 4 pmol/106 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.
AB - 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/106 cells/hr v 10 ± 4 pmol/106 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.
KW - Glomerulonephritis
KW - low-density lipoprotein
KW - macrophages
KW - oxidized low-density lipoprotein
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U2 - 10.1016/0272-6386(95)90658-4
DO - 10.1016/0272-6386(95)90658-4
M3 - Article
C2 - 7645542
AN - SCOPUS:0029143883
SN - 0272-6386
VL - 26
SP - 362
EP - 367
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 2
ER -