Glomerular macrophages produce reactive oxygen species in experimental glomerulonephritis.
The production of reactive oxygen species by intraglomerular macrophages was assessed in a macrophage dependent model of diffuse proliferative glomerulonephritis in rabbits. Glomerular 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/10(6) cells), H2O2 (4.4 +/- 2.5 nmol/hr/10(6) cells) and OH. (57.8 +/- 4.7 U/hr/10(6) 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/10(6) cells; H2O2 0.6 +/- 0.3 nmol/hr/10(6) cells; OH. 11.0 +/- 1.8 U/hr/10(6) cells; blood monocytes, O2- 8.6 +/- 1.4 nmol/hr/10(6) cells; OH. 9.9 +/- 1.2 U/hr/10(6) cells, (all P less than 0.05 cf. glom macs). Hydrogen peroxide production by blood monocytes (1.6 +/- 0.9 nmol/hr/10(6) 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.
Boyce
N W
NW
Monash University, Department of Medicine, Prince Henry's Hospital, Melbourne, Australia.
Tipping
P G
PG
Holdsworth
S R
SR
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001323:Autoantibodies; D005609:Free Radicals; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D007678:Kidney Glomerulus / Q000166:cytology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D011650:Pulmonary Alveoli / Q000166:cytology; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism*
D000906:Antibodies; D001323:Autoantibodies; D005609:Free Radicals; D006878:Hydroxides; C051951:antiglomerular basement membrane antibody; D013481:Superoxides; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide