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The requirement for granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in
A Richard Kitching1, Xiao Ru Huang1, Amanda L Turner1
1*Centre for Inflammatory Diseases, Monash University, Department of Medicine, Monash Medical Centre, Clayton, Australia; Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Insights
Endogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) is crucial in experimental glomerulonephritis. GM-CSF deficiency protected mice from both early and later stages of kidney injury, unlike G-CSF deficiency.
Area of Science:
- Nephrology
- Immunology
- Hematology
Background:
- Proliferative glomerulonephritis involves leukocytes in glomeruli.
- Colony-stimulating factors like GM-CSF and G-CSF influence immune cell function.
Purpose of the Study:
- To investigate the roles of GM-CSF and G-CSF in leukocyte-mediated glomerulonephritis.
- To determine the impact of GM-CSF and G-CSF deficiency on distinct phases of kidney injury.
Main Methods:
- Utilized genetically modified mice lacking GM-CSF (GM-CSF -/-) or G-CSF (G-CSF -/-).
- Studied two models: neutrophil-mediated heterologous-phase anti-GBM glomerulonephritis and T cell/macrophage-mediated crescentic autologous-phase anti-GBM glomerulonephritis.
Main Results:
- Both GM-CSF -/- and G-CSF -/- mice showed protection against heterologous-phase injury, with reduced proteinuria and neutrophils.
- Only GM-CSF -/- mice were protected from crescentic injury; G-CSF -/- mice had increased glomerular T cells.
- Humoral responses were unaffected, but GM-CSF deficiency reduced glomerular T cells, macrophages, and delayed-type hypersensitivity.
Conclusions:
- Endogenous GM-CSF plays a significant role in both autologous and heterologous phases of experimental glomerulonephritis.
- GM-CSF, but not G-CSF, is critical for T cell and macrophage-mediated crescentic glomerulonephritis.
- Targeting GM-CSF may offer therapeutic potential for specific types of glomerulonephritis.
Abstract:
Proliferative glomerulonephritis in humans is characterized by the presence of leukocytes in glomeruli. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) can potentially stimulate or affect T cell, macrophage, and neutrophil function. To define the roles of GM-CSF and G-CSF in leukocyte-mediated glomerulonephritis, glomerular injury was studied in mice genetically deficient in either GM-CSF (GM-CSF -/- mice) or G-CSF (G-CSF -/- mice). Two models of glomerulonephritis were studied: neutrophil-mediated heterologous-phase anti-glomerular basement membrane (GBM) glomerulonephritis and T cell/macrophage-mediated crescentic autologous-phase anti-GBM glomerulonephritis. Both GM-CSF -/- and G-CSF -/- mice were protected from heterologous-phase anti-GBM glomerulonephritis compared with genetically normal (CSF WT) mice, with reduced proteinuria and glomerular neutrophil numbers. However, only GM-CSF -/- mice were protected from crescentic glomerular injury in the autologous phase, whereas G-CSF -/- mice were not protected and in fact had increased numbers of T cells in glomeruli. Humoral responses to the nephritogenic antigen were unaltered by deficiency of either GM-CSF or G-CSF, but glomerular T cell and macrophage numbers, as well as dermal delayed-type hypersensitivity to the nephritogenic antigen, were reduced in GM-CSF -/- mice. These studies demonstrate that endogenous GM-CSF plays a role in experimental glomerulonephritis in both the autologous and heterologous phases of injury.