The requirement for granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in leukocyte-mediated immune glomerular injury. 2002

A Richard Kitching, and Xiao Ru Huang, and Amanda L Turner, and Peter G Tipping, and Ashley R Dunn, and Stephen R Holdsworth
*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.

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.

UI MeSH Term Description Entries
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D006736 Horses Large, hoofed mammals of the family EQUIDAE. Horses are active day and night with most of the day spent seeking and consuming food. Feeding peaks occur in the early morning and late afternoon, and there are several daily periods of rest. Equus caballus,Equus przewalskii,Horse, Domestic,Domestic Horse,Domestic Horses,Horse,Horses, Domestic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012712 Serum Globulins All blood proteins except albumin ( Euglobulin,Euglobulins,Pseudoglobulin,Pseudoglobulins,Serum Globulin,Globulin, Serum,Globulins, Serum
D012756 Sheep Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS. Ovis,Sheep, Dall,Dall Sheep,Ovis dalli
D015432 Glomerulonephritis, Membranoproliferative Chronic glomerulonephritis characterized histologically by proliferation of MESANGIAL CELLS, increase in the MESANGIAL EXTRACELLULAR MATRIX, and a thickening of the glomerular capillary walls. This may appear as a primary disorder or secondary to other diseases including infections and autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Various subtypes are classified by their abnormal ultrastructures and immune deposits. Hypocomplementemia is a characteristic feature of all types of MPGN. C3G Complement 3 Glomerulopathy,Complement 3 Glomerulopathies,Complement 3 Glomerulopathy,Glomerulonephritis, Mesangiocapillary,MPGN Membranoproliferative Glomerulonephritis,Membranoproliferative Glomerulonephritis,Mesangiocapillary Glomerulonephritis,DDD MPGNII,Dense Deposit Disease,Glomerulonephritis, Hypocomplementemic,MPGNII,Membranoproliferative Glomerulonephritis Type II,Membranoproliferative Glomerulonephritis, Type I,Membranoproliferative Glomerulonephritis, Type II,Membranoproliferative Glomerulonephritis, Type III,Mesangiocapillary Glomerulonephritis, Type I,Mesangiocapillary Glomerulonephritis, Type II,Subendothelial Membranoproliferative Glomerulonephritis,Type II MPGN,DDD MPGNIIs,Glomerulonephritides, MPGN Membranoproliferative,Glomerulonephritides, Membranoproliferative,Glomerulonephritis, MPGN Membranoproliferative,Glomerulopathies, Complement 3,Glomerulopathy, Complement 3,Hypocomplementemic Glomerulonephritides,Hypocomplementemic Glomerulonephritis,MPGN Membranoproliferative Glomerulonephritides,MPGN, Type II,MPGNII, DDD,MPGNIIs,Membranoproliferative Glomerulonephritides,Membranoproliferative Glomerulonephritides, MPGN,Membranoproliferative Glomerulonephritis, MPGN,Membranoproliferative Glomerulonephritis, Subendothelial,Mesangiocapillary Glomerulonephritides,Type II MPGNs
D016178 Granulocyte-Macrophage Colony-Stimulating Factor An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. CSF-GM,Colony-Stimulating Factor, Granulocyte-Macrophage,GM-CSF,Histamine-Producing Cell-Stimulating Factor,CSF-2,TC-GM-CSF,Tumor-Cell Human GM Colony-Stimulating Factor,Cell-Stimulating Factor, Histamine-Producing,Colony Stimulating Factor, Granulocyte Macrophage,Granulocyte Macrophage Colony Stimulating Factor,Histamine Producing Cell Stimulating Factor,Tumor Cell Human GM Colony Stimulating Factor
D016179 Granulocyte Colony-Stimulating Factor A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. Colony-Stimulating Factor, Granulocyte,G-CSF,Myeloid Growth Factor,Colony Stimulating Factor, Granulocyte,Factor, Granulocyte Colony-Stimulating,Factor, Myeloid Growth,Granulocyte Colony Stimulating Factor,Growth Factor, Myeloid
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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