Glomerular expression of macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in patients with various forms of glomerulonephritis

Macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are major mediators for the differentiation, proliferation, and activation of the macrophage. Recently, M-CSF was documented to play a pivotal role in the development of nephritis via macrophage activation in MRL-Ipr mice. The macrophage is also considered to be an important component in the development of human glomerulonephritis. The expression and function of colonystimulating factors (CSF) in the human kidney have not yet been defined. This study was undertaken to elucidate the various roles of CSF in the development of glomerulonephritis in humans. We examined the glomerular expression of M-CSF and GM-CSF in patients with various forms of glomerulonephritis and in normal subjects using immunohistochemical methods and nonradio-isotopic in situ hybridization. The expression of CSF at both the protein and mRNA level in the glomeruli was compared with the degree of mesangial proliferation; the number of macrophages, Ki67-positive cells, and HLA-DR-positive cells; and the degree of α-smooth muscle actin-positive area in the glomerulus and clinical data. M-CSF and GM-CSF were expressed mainly on the mesangial cells in the glomerulus. Intraglomerular expressions of CSF at the protein level were increased in cases of IgA nephropathy and lupus nephritis. There was a positive correlation among the M-CSF protein expression and glomerular proliferation, macrophage infiltration, and the degree of proteinuria. M-CSF mRNA expression also was increased in the cases of IgA nephropathy and lupus nephritis. The number of Ki67-positive cells and HLA-DR-positive cells and α-smooth muscle actin-positive area in the glomerulus were increased in the cases with enhanced M-CSF expression. These results suggest that the glomerular secretion of M-CSF promotes macrophage infiltration into the glomerulus and activates resident and extraneous macrophages in the mesangial proliferative glomerulonephritis. M-CSF is considered to be a major mediator in the development of mesangial proliferative glomerulonephritis in humans.