We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Important role for macrophages in induction of crescentic anti-GBM glomerulonephritis in WKY rats.
- Authors
Masato Isome; Hidehiko Fujinaka; Laxman P. Adhikary; Pavel Kovalenko; Adel G. Ahmed El-Shemi; Yutaka Yoshida; Eishin Yaoita; Toshiyuki Takeishi; Motohiro Takeya; Makoto Naito; Hitoshi Suzuki; Tadashi Yamamoto
- Abstract
Background. 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/Mϕ), 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/Mϕ in the development of anti-GBM GN.Methods. We examined correlations between the amount of urinary protein and the numbers of glomerular CD8+ cells or Mo/Mϕ in rats after administrating different doses of anti-GBM antibody (5.0, 7.5, 10.0 and 25.0?l/100?g body weight). The roles of Mo/Mϕ in induction of GN were examined in animals by depleting Mo/Mϕ 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.Results. Liposome-MDP treatment significantly reduced the number of ED-1+ Mo/Mϕ accumulated in glomeruli from 32.11.2 to 1.40.3/glomerular cross-section (meanSD, P<0.01), and the amount of urinary protein from 103.819.8 to 31.815.9?mg/day (P<0.01), as well as the incidence of crescentic glomeruli from 91.32.7 to 23.37.6% (P<0.01) at day 8. This treatment also reduced the number of CD8+ cells accumulating in the glomeruli from 5.4 0.7 to 0.50.1/glomerular cross-section (P<0.01). Upregulation of glomerular intercellular adhesion molecule 1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1) mRNA expression was suppressed by Mo/Mϕ depletion.Conclusion. These results indicate that Mo/Mϕ play an important role in the induction of crescentic anti-GBM GN and glomerular injury.
- Subjects
MACROPHAGES; CELLS; LEUCOCYTES; KILLER cells; KIDNEY diseases; URINALYSIS
- Publication
Nephrology Dialysis Transplantation, 2004, Vol 19, Issue 12, p2997
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfh558