Important role for macrophages in induction of crescentic anti-GBM glomerulonephritis in WKY rats
| Autor: | Adel Galal El-Shemi, Tadashi Yamamoto, Toshiyuki Takeishi, Hidehiko Fujinaka, Laxman P. Adhikary, Hitoshi Suzuki, Motohiro Takeya, Yutaka Yoshida, Makoto Naito, Pavel Kovalenko, Eishin Yaoita, Masato Isome |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
medicine.medical_specialty
Kidney Glomerulus CD8-Positive T-Lymphocytes urologic and male genital diseases Rats Inbred WKY Antibodies Basement Membrane Glomerulonephritis Internal medicine medicine Macrophage Animals Receptor Basement membrane Transplantation biology urogenital system business.industry Monocyte Macrophages medicine.disease Immunohistochemistry female genital diseases and pregnancy complications Rats Disease Models Animal Proteinuria Endocrinology medicine.anatomical_structure Nephrology biology.protein Female Antibody business CD8 |
| Zdroj: | Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 19(12) |
| ISSN: | 0931-0509 |
| Popis: | A crucial role for CD8(+) cells in induction of crescentic anti-glomerular basement membrane (GBM) glomerulonephritis (GN) in WKY rats was demonstrated in studies showing that depletion of CD8(+) cells completely suppressed glomerular accumulation of monocytes/macrophages (Mo/Mphi), crescent formation and proteinuria. Because these studies did not definitively identify CD8(+) cells as the cause of tissue injury, we examined the roles of Mo/Mphi in the development of anti-GBM GN.We examined correlations between the amount of urinary protein and the numbers of glomerular CD8(+) cells or Mo/Mphi in rats after administrating different doses of anti-GBM antibody (5.0, 7.5, 10.0 and 25.0 microl/100 g body weight). The roles of Mo/Mphi in induction of GN were examined in animals by depleting Mo/Mphi in the glomerulus. To do this, rats were injected intravenously with liposome-encapsulated dichloromethylene diphosphonate (liposome-MDP) from day 3 to day 7 after anti-GBM antibody injection and they were then sacrificed at day 8.Liposome-MDP treatment significantly reduced the number of ED-1(+) Mo/Mphi accumulated in glomeruli from 32.1 +/- 1.2 to 1.4 +/- 0.3/glomerular cross-section (mean +/- SD, P0.01), and the amount of urinary protein from 103.8 +/- 19.8 to 31.8 +/- 15.9 mg/day (P0.01), as well as the incidence of crescentic glomeruli from 91.3 +/- 2.7 to 23.3 +/- 7.6% (P0.01) at day 8. This treatment also reduced the number of CD8(+) cells accumulating in the glomeruli from 5.4 +/- 0.7 to 0.5 +/- 0.1/glomerular cross-section (P0.01). Upregulation of glomerular intercellular adhesion molecule 1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1) mRNA expression was suppressed by Mo/Mphi depletion.These results indicate that Mo/Mphi play an important role in the induction of crescentic anti-GBM GN and glomerular injury. |
| Databáze: | OpenAIRE |
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