MACROPHAGE-COLONY-STIMULATING FACTOR (M-CSF) ENHANCES PROTEINURIA ANDRECRUITMENT OF MACROPHAGES INTO THE GLOMERULUS IN EXPERIMENTAL MURINENEPHRITIS

In this study, we examined the effects of macrophage-colony stimulatin g factor (M-CSF) on glomerular macrophages in lipopolysaccharide (LPS) -induced murine nephritis. Mice injected intraperitoneally with either M-CSF plus LPS, LPS alone, M-CSF alone or saline every day for 8 days were examined for the degree of urine albumin excretion and lymphocyt e-function associated antigen-1-positive (LFA-1(+)) cells in periphera l blood as well as renal pathology. From our results, LPS or M-CSF com bined with LPS emphasized the degree of proteinuria, glomerular deposi tion of immunoglobulins and mesangial proliferation, associated with a ccumulation of macrophages in the glomeruli. However, in immunohistolo gical examination of kidneys from these nephritic mice, neither interc ellular adhesion molecule-1 (ICAM-1), which may play an important role in the recruitment of macrophages into glomeruli, M-CSF receptor nor the number of LFA-1(+) cells in peripheral blood was enhanced by M-CSF . On the other hand, M-CSF alone induced neither proteinuria nor any p athological changes and did not increase the number of glomerular Mac- 1(+) cells above that in saline-treated controls. These results indica te that M-CSF does not directly cause glomerulonephritis but might par ticipate in accelerating the glomerular inflammatory process by stimul ating a potent chemoattractant to recruit monocytes-macrophages into t he glomeruli.