| First Author | Timoshanko JR | Year | 2005 |
| Journal | J Am Soc Nephrol | Volume | 16 |
| Issue | 9 | Pages | 2646-56 |
| PubMed ID | 16033860 | Mgi Jnum | J:114300 |
| Mgi Id | MGI:3688757 | Doi | 10.1681/ASN.2004121107 |
| Citation | Timoshanko JR, et al. (2005) Granulocyte macrophage colony-stimulating factor expression by both renal parenchymal and immune cells mediates murine crescentic glomerulonephritis. J Am Soc Nephrol 16(9):2646-56 |
| abstractText | GM-CSF has previously been demonstrated to be important in crescentic glomerulonephritis (GN). As both renal parenchymal cells and infiltrating inflammatory cells produce GM-CSF, their separate contributions to inflammatory renal injury were investigated by creation of two different types of GM-CSF chimeric mice: (1) GM-CSF-deficient (GM-CSF-/-)-->wild-type (WT) chimeras with leukocytes that are unable to produce GM-CSF and (2) WT-->GM-CSF-/- chimeras with deficient renal cell GM-CSF expression. Crescentic anti-glomerular basement membrane GN was induced in WT, GM-CSF(-/-)-->WT chimeras, WT-->GM-CSF-/- chimeras, and GM-CSF-/- mice by planting an antigen (sheep globulin) in their glomeruli. WT mice developed severe crescentic GN, whereas GM-CSF-/- were protected from development of disease. Glomerular T cell recruitment, CD40+ glomerular cells, and renal IFN-gamma and TNF expression were similar in both chimeras and WT mice but significantly reduced in GM-CSF-/- mice, indicating that either leukocyte or renal sources of GM-CSF are sufficient to drive these aspects of the inflammatory response. Restricted expression of GM-CSF revealed a major role for renal cell-derived GM-CSF but a minor role for leukocyte-derived GM-CSF in the formation of cellular crescents; glomerular MHC II expression; serum creatinine; and monocyte chemoattractant protein-1, vascular cellular adhesion molecule, and IL-1beta expression. Glomerular macrophage accumulation, proteinuria, and interstitial infiltrate were equivalent in both chimeric groups but intermediate between WT and GM-CSF-/-, indicating that both sources are required for the full development of glomerular injury in crescentic GN. |
