title: The requirement for granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in leukocyte-mediated immune glomerular injury.
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.
authors.affiliation: *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.
authors.forename: A Richard
authors.initials: AR
authors.lastname: Kitching
authors.affiliation: *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.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ru Huang
authors.affiliation: *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.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Turner
authors.affiliation: *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.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Tipping
authors.affiliation: *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.
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Dunn
authors.affiliation: *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.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Holdsworth
mesh_terms: D000818:Animals; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology* / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006736:Horses / Q000097:blood; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout / Q000235:genetics; D009504:Neutrophils / Q000276:immunology*; D012712:Serum Globulins / Q000276:immunology; D012756:Sheep / Q000097:blood
chemical_list: D012712:Serum Globulins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor