Glomerular macrophages produce reactive oxygen species in experimental glomerulonephritis

Abstract

The production of reactive oxygen species by intraglomerular macrophages was assessed in a macrophage dependent model of diffuse proliferative glomerulonephritis in rabbits. Glonerular macrophages were obtained from isolated nephritic glomeruli by short term (60 min) culture. Control macrophage populations were simultaneously obtained from peripheral blood (blood monocytes) and lung lavage fluid (alveolar macrophages). Superoxide anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical (OH.) production was assessed. Glomerular macrophage production of O2- (48.9 ± 5.5 nmol/hr/106 cells), H2O2 (4.4 ± 2.5 nmol/hr/106 cells) and OH. (57.8 ± 4.7 U/hr/106 cells) was significantly greater than the production of reactive oxygen species seen with control monocyte populations: alveolar macrophages, O2- 9.8 ± 2.0 nmol/hr/106 cells; H2O2 0.6 ± 0.3 nmol/hr/106 cells; OH. 11.0 ± 1.8 U/hr/106 cells; blood monocytes, O2- 8.6 ± 1.4 nmol/hr/106 cells; OH. 9.9 ± 1.2 U/hr/106 cells, (all P < 0.05 cf. glom macs). Hydrogen peroxide production by blood monocytes (1.6 ± 0.9 nmol/hr/106 cells) was less than glomerular macrophages; however, this difference was not statistically significant. The enhanced production of reactive oxygen species by glomerular macrophages in this macrophage dependent model of glomerulonephritis suggests that these mononuclear cells are locally activated within the glomerulus following recruitment from the circulation. Reactive oxygen species production by glomerular macrophages may contribute to their ability to induce glomerular basement membrane injury in this disease.