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Published in: Clinical and Experimental Nephrology 2/2010

01-04-2010 | Original Article

Granulomatous transformation of capillary lesions in pulmonary-renal syndrome autologously induced anti-glomerular basement membrane disease in Wistar–Kyoto rats

Authors: Daiju Aoyagi, Koh Nakazawa, Tomoki Kaneyama, Junya Masumoto, Masako Otani, Hidekazu Shigematsu

Published in: Clinical and Experimental Nephrology | Issue 2/2010

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Abstract

Background

Pulmonary-renal syndrome is characterized by pulmonary hemorrhage and rapidly progressive glomerulonephritis in various immunological states. Histopathological analysis of pulmonary-renal syndrome is not yet complete.

Methods

Wistar–Kyoto (WKY) rats were sensitized using the noncollagenous (NC1) domain of type IV collagen from bovine kidney as an antigen. Histopathology of the kidneys and lungs was investigated with light microscopy, immunohistochemistry and electromicroscopy. Expression levels of cytokine mRNA were determined by real-time RT-PCR using renal tissue of rats.

Results

Macrophage-rich granulomatous glomerulonephritis and alveolar capillaritis accompanied with pulmonary hemorrhage were induced by the sensitization. The humoral antibody against NC1 was detected on the glomerular and alveolar capillary walls. Th2 cytokine IL-10 was dominant over Th1 cytokine IFN-γ in renal tissues of WKY rats.

Conclusion

The granulomatous transformation seemed to be induced by macrophage conspicuous capillaritis under dominant cellular immune reactions in WKY rats. In addition to Th1 cytokines, Th2 cytokines may also participate in the formation of granulomatous lesions.
Literature
1.
go back to reference Glassock RJ, Cohen AH, Adler SG, Ward HJ. Goodpasture’s disease. In: Brenner BM, Rector FC, editors. The kidney. 4th ed. Philadelphia: WB Saunders; 1991. p. 1301–5. Glassock RJ, Cohen AH, Adler SG, Ward HJ. Goodpasture’s disease. In: Brenner BM, Rector FC, editors. The kidney. 4th ed. Philadelphia: WB Saunders; 1991. p. 1301–5.
2.
go back to reference Shigematsu H, Kobayashi Y. Pulmonary involvements in the initial phase of rat Masugi nephritis. Virchows Arch B Cell Pathol. 1972;11:111–23.PubMed Shigematsu H, Kobayashi Y. Pulmonary involvements in the initial phase of rat Masugi nephritis. Virchows Arch B Cell Pathol. 1972;11:111–23.PubMed
3.
go back to reference Shigematsu H. Glomerular events during the initial phase of rat Masugi nephritis. Virchows Arch B Cell Pathol. 1970;5:187–200.PubMed Shigematsu H. Glomerular events during the initial phase of rat Masugi nephritis. Virchows Arch B Cell Pathol. 1970;5:187–200.PubMed
4.
go back to reference Kawasaki K, Yaoita E, Yamamoto T, Kihara I. Depletion of CD8 positive cells in nephrotoxic serum nephritis of WKY rats. Kidney Int. 1992;41:1517–26.CrossRefPubMed Kawasaki K, Yaoita E, Yamamoto T, Kihara I. Depletion of CD8 positive cells in nephrotoxic serum nephritis of WKY rats. Kidney Int. 1992;41:1517–26.CrossRefPubMed
5.
go back to reference Abbate M, Kalluri R, Corna D, Yamaguchi N, McCluskey RT, Hudson BG, et al. Experimental Goodpasture’s syndrome in Wistar–Kyoto rats immunized with α3 chain of type IV collagen. Kidney Int. 1998;54:1550–61. Abbate M, Kalluri R, Corna D, Yamaguchi N, McCluskey RT, Hudson BG, et al. Experimental Goodpasture’s syndrome in Wistar–Kyoto rats immunized with α3 chain of type IV collagen. Kidney Int. 1998;54:1550–61.
6.
go back to reference Hoffmann KF, Caspar P, Cheever AW, Wynn TA. IFN-γ, IL-12, and TNF-α are required to maintain reduced liver pathology in mice vaccinated with Schistosoma mansoni eggs and IL-12. J Immunol. 1998;161:4201–10.PubMed Hoffmann KF, Caspar P, Cheever AW, Wynn TA. IFN-γ, IL-12, and TNF-α are required to maintain reduced liver pathology in mice vaccinated with Schistosoma mansoni eggs and IL-12. J Immunol. 1998;161:4201–10.PubMed
7.
go back to reference Müller A, Trabandt A, Gloeckner-Hofmann K, Seitzer U, Csernok E, Schönermarck U, et al. Localized Wegener’s granulomatosis: predominance of CD26 and IFN-γ expression. J Pathol. 2000;192:113–20.CrossRefPubMed Müller A, Trabandt A, Gloeckner-Hofmann K, Seitzer U, Csernok E, Schönermarck U, et al. Localized Wegener’s granulomatosis: predominance of CD26 and IFN-γ expression. J Pathol. 2000;192:113–20.CrossRefPubMed
8.
go back to reference Shigematsu H, Kobayashi Y. The development and fate of the immune deposits in the glomerulus during the secondary phase of rat Masugi nephritis. Virchows Arch B Cell Pathol. 1971;8:83–95.PubMed Shigematsu H, Kobayashi Y. The development and fate of the immune deposits in the glomerulus during the secondary phase of rat Masugi nephritis. Virchows Arch B Cell Pathol. 1971;8:83–95.PubMed
9.
go back to reference Mukai K, Shibata T, Kato K, Sugisaki T. Adjuvant-induced macrophage-dominant nephrotoxic serum nephritis in rats. Clin Exp Nephrol. 2005;9:15–23.CrossRefPubMed Mukai K, Shibata T, Kato K, Sugisaki T. Adjuvant-induced macrophage-dominant nephrotoxic serum nephritis in rats. Clin Exp Nephrol. 2005;9:15–23.CrossRefPubMed
10.
go back to reference Leatherman JW, Sibley RK, Davies SF. Diffuse intrapulmonary hemorrhage and glomerulonephritis unrelated to anti-glomerular basement membrane antibody. Am J Med. 1982;72:401–10.CrossRefPubMed Leatherman JW, Sibley RK, Davies SF. Diffuse intrapulmonary hemorrhage and glomerulonephritis unrelated to anti-glomerular basement membrane antibody. Am J Med. 1982;72:401–10.CrossRefPubMed
11.
go back to reference Churg J, Bernstein J, Glassock RJ. Glomerular lesions in vascular diseases. In: Churg J, Bernstein J, Glassock RJ, editors. Renal diseases: classification and atlas of glomerular diseases. 2nd ed. New York: Igaku-shoin; 1995. p. 255–71. Churg J, Bernstein J, Glassock RJ. Glomerular lesions in vascular diseases. In: Churg J, Bernstein J, Glassock RJ, editors. Renal diseases: classification and atlas of glomerular diseases. 2nd ed. New York: Igaku-shoin; 1995. p. 255–71.
12.
go back to reference Akikusa B, Sato T, Ogawa M, Ueda S, Kondo Y. Necrotizing alveolar capillaritis in autopsy cases of microscopic polyangitis. Incidence, histopathogenesis, and relationship with systemic vasculitis. Arch Pathol Lab Med. 1997;121:144–9.PubMed Akikusa B, Sato T, Ogawa M, Ueda S, Kondo Y. Necrotizing alveolar capillaritis in autopsy cases of microscopic polyangitis. Incidence, histopathogenesis, and relationship with systemic vasculitis. Arch Pathol Lab Med. 1997;121:144–9.PubMed
13.
go back to reference Bajema IM, Hagen EC, Ferrario F, Waldherr R, Noel LH, Hermans J, et al. Renal granulomas in systemic vasculitis. Clin Nephrol. 1997;48:16–21.PubMed Bajema IM, Hagen EC, Ferrario F, Waldherr R, Noel LH, Hermans J, et al. Renal granulomas in systemic vasculitis. Clin Nephrol. 1997;48:16–21.PubMed
14.
go back to reference Cunningham MA, Huang XR, Dowling JP, Tipping PG, Holdsworth SR. Prominence of cell-mediated immunity effectors in “pauci-immune” glomerulonephritis. J Am Soc Nephrol. 1999;10:499–506.PubMed Cunningham MA, Huang XR, Dowling JP, Tipping PG, Holdsworth SR. Prominence of cell-mediated immunity effectors in “pauci-immune” glomerulonephritis. J Am Soc Nephrol. 1999;10:499–506.PubMed
15.
go back to reference Horio T. Development and fate of crescentic and granulomatous lesions in rat Masugi nephritis. Pathol Int. 2001;51:72–81.CrossRefPubMed Horio T. Development and fate of crescentic and granulomatous lesions in rat Masugi nephritis. Pathol Int. 2001;51:72–81.CrossRefPubMed
16.
go back to reference Holdsworth S, Kitching AR, Tipping PG. Th1 and Th2 T helper cell subsets affect patterns of injury and outcomes in glomerulonephritis. Kidney Int. 1999;55:1198–216.CrossRefPubMed Holdsworth S, Kitching AR, Tipping PG. Th1 and Th2 T helper cell subsets affect patterns of injury and outcomes in glomerulonephritis. Kidney Int. 1999;55:1198–216.CrossRefPubMed
17.
go back to reference Huang XR, Holdsworth SR, Tipping PG. Evidence for delayed-type hypersensitivity mechanisms in glomerular crescent formation. Kidney Int. 1994;46:69–78.CrossRefPubMed Huang XR, Holdsworth SR, Tipping PG. Evidence for delayed-type hypersensitivity mechanisms in glomerular crescent formation. Kidney Int. 1994;46:69–78.CrossRefPubMed
18.
go back to reference Tipping PG, Huang XR, Qi M, Van GY, Tang WW. Crescentic glomerulonephritis in CD4- and CD8-deficient mice. Requirement for CD4 but not CD8 cells. Am J Pathol. 1998;152:1541–8.PubMed Tipping PG, Huang XR, Qi M, Van GY, Tang WW. Crescentic glomerulonephritis in CD4- and CD8-deficient mice. Requirement for CD4 but not CD8 cells. Am J Pathol. 1998;152:1541–8.PubMed
19.
go back to reference Huang XR, Tipping PG, Shuo L, Holdsworth SR. Th1 responsiveness to nephritogenic antigens determines susceptibility to crescentic glomerulonephritis in mice. Kidney Int. 1997;51:94–103.CrossRefPubMed Huang XR, Tipping PG, Shuo L, Holdsworth SR. Th1 responsiveness to nephritogenic antigens determines susceptibility to crescentic glomerulonephritis in mice. Kidney Int. 1997;51:94–103.CrossRefPubMed
20.
go back to reference Coelho SN, Saleem S, Konieczny BT, Parekh KR, Baddoura FK, Lakkis FG. Immunologic determinants of susceptibility to experimental glomerulonephritis. Role of cellular immunity. Kidney Int. 1997;51:646–52.CrossRefPubMed Coelho SN, Saleem S, Konieczny BT, Parekh KR, Baddoura FK, Lakkis FG. Immunologic determinants of susceptibility to experimental glomerulonephritis. Role of cellular immunity. Kidney Int. 1997;51:646–52.CrossRefPubMed
21.
go back to reference Hopfer H, Maron R, Butzmann U, Helmchen U, Weiner HL, Kalluri R. The importance of cell-mediated immunity in the course and severity of autoimmune anti-glomerular basement membrane disease in mice. FASEB J. 2003;17:860–8.CrossRefPubMed Hopfer H, Maron R, Butzmann U, Helmchen U, Weiner HL, Kalluri R. The importance of cell-mediated immunity in the course and severity of autoimmune anti-glomerular basement membrane disease in mice. FASEB J. 2003;17:860–8.CrossRefPubMed
22.
go back to reference Kitching AR, Turner AL, Semple T, Li M, Edgtton KL, Wilson GR, et al. Experimental autoimmune anti-glomerular basement membrane glomerulonephritis: a protective role for IFN-γ. J Am Soc Nephrol. 2004;15:1764–74.CrossRefPubMed Kitching AR, Turner AL, Semple T, Li M, Edgtton KL, Wilson GR, et al. Experimental autoimmune anti-glomerular basement membrane glomerulonephritis: a protective role for IFN-γ. J Am Soc Nephrol. 2004;15:1764–74.CrossRefPubMed
23.
go back to reference Reynolds J, Norgan VA, Bhambra U, Smith J, Cook HT, Pusey CD. Anti-CD8 monoclonal antibody therapy is effective in the prevention and treatment of experimental autoimmune glomerulonephritis. J Am Soc Nephrol. 2002;13:359–69.PubMed Reynolds J, Norgan VA, Bhambra U, Smith J, Cook HT, Pusey CD. Anti-CD8 monoclonal antibody therapy is effective in the prevention and treatment of experimental autoimmune glomerulonephritis. J Am Soc Nephrol. 2002;13:359–69.PubMed
24.
go back to reference Ladel CH, Flesch IEA, Arnoldi J, Kaufmann SHE. Studies with MHC-deficient knock-out mice reveal impact of both MHC I- and MHC II-dependent T cell responses on Listeria monocytogenes infection. J Immunol. 1994;153:3116–22. Ladel CH, Flesch IEA, Arnoldi J, Kaufmann SHE. Studies with MHC-deficient knock-out mice reveal impact of both MHC I- and MHC II-dependent T cell responses on Listeria monocytogenes infection. J Immunol. 1994;153:3116–22.
25.
go back to reference Stenger S, Rosat JP, Bloom BR, Krensky AM, Modlin RL. Granulysin: a lethal weapon of cytolytic T cells. Immunol Today. 1999;20:390–4.CrossRefPubMed Stenger S, Rosat JP, Bloom BR, Krensky AM, Modlin RL. Granulysin: a lethal weapon of cytolytic T cells. Immunol Today. 1999;20:390–4.CrossRefPubMed
Metadata
Title
Granulomatous transformation of capillary lesions in pulmonary-renal syndrome autologously induced anti-glomerular basement membrane disease in Wistar–Kyoto rats
Authors
Daiju Aoyagi
Koh Nakazawa
Tomoki Kaneyama
Junya Masumoto
Masako Otani
Hidekazu Shigematsu
Publication date
01-04-2010
Publisher
Springer Japan
Published in
Clinical and Experimental Nephrology / Issue 2/2010
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-009-0260-9

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