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Glomerular macrophages produce reactive oxygen species in experimental glomerulonephritis
N W Boyce1, P G Tipping, S R Holdsworth
1Monash University, Department of Medicine, Prince Henry's Hospital, Melbourne, Australia.
Abstract:
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.
Insights
Glomerular macrophages in rabbits produce significantly more reactive oxygen species than other macrophage types, indicating local activation and potential contribution to kidney injury in glomerulonephritis.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Diffuse proliferative glomerulonephritis is a kidney disease involving inflammation of the glomeruli.
- Macrophages play a key role in the pathogenesis of glomerulonephritis.
- The specific role of intraglomerular macrophages in producing reactive oxygen species (ROS) in this condition requires further elucidation.
Purpose of the Study:
- To investigate and compare the production of reactive oxygen species (ROS) by intraglomerular macrophages versus control macrophage populations (alveolar and blood monocytes) in a rabbit model of glomerulonephritis.
- To determine if intraglomerular macrophages exhibit enhanced ROS production, suggesting local activation.
Main Methods:
- A macrophage-dependent model of diffuse proliferative glomerulonephritis was established in rabbits.
- Glomerular macrophages were isolated from nephritic glomeruli.
- Control macrophage populations were obtained from peripheral blood (monocytes) and lung lavage fluid (alveolar macrophages).
- Production of superoxide anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (OH.) was measured in all macrophage populations.
Main Results:
- Glomerular macrophages exhibited significantly higher production of O2-, H2O2, and OH. compared to alveolar macrophages and blood monocytes (P < 0.05).
- Specifically, glomerular macrophages produced 48.9 nmol/hr/10(6) cells O2-, 4.4 nmol/hr/10(6) cells H2O2, and 57.8 U/hr/10(6) cells OH..
- While blood monocytes showed lower H2O2 production than glomerular macrophages, this difference was not statistically significant.
Conclusions:
- Intraglomerular macrophages in this glomerulonephritis model demonstrate significantly enhanced production of reactive oxygen species.
- This heightened ROS production suggests that these macrophages are activated locally within the glomerulus after being recruited from the circulation.
- The ROS generated by activated glomerular macrophages may contribute to glomerular basement membrane injury in this disease model.