Glomerular macrophages in nephrotoxic serum nephritis are activated to oxidize low-density lipoprotein

Jonathan Rie, Sharon Silbiger, Joel Neugarten

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)362-367
Number of pages6
JournalAmerican Journal of Kidney Diseases
Volume26
Issue number2
DOIs
StatePublished - Aug 1995

Keywords

  • Glomerulonephritis
  • low-density lipoprotein
  • macrophages
  • oxidized low-density lipoprotein

ASJC Scopus subject areas

  • Nephrology

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