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

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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.

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Acknowledgments

This work was supported in part by Grant-in-Aid for Scientific Research C-18590524 from the Japan Society for the Promotion of Science (to JM). The authors are grateful to members of the Department of Pathology, Shinshu University School of Medicine, for their encouragement and helpful discussions during this study, and to Ms. Tomoko Nishizawa and Ms. Matsuko Watanabe for their technical assistance.

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Authors and Affiliations

  1. Department of Pathology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Daiju Aoyagi, Tomoki Kaneyama, Junya Masumoto, Masako Otani & Hidekazu Shigematsu

  2. Department of Laboratory Medicine, Matsumoto Medical Center Matsumoto Hospital, 1209 Yoshikawa Murai-cho, Matsumoto, 399-8701, Japan

    Koh Nakazawa

Authors
  1. Daiju Aoyagi
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  2. Koh Nakazawa
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  3. Tomoki Kaneyama
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  4. Junya Masumoto
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  5. Masako Otani
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  6. Hidekazu Shigematsu
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Correspondence to Koh Nakazawa.

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Aoyagi, D., Nakazawa, K., Kaneyama, T. et al. Granulomatous transformation of capillary lesions in pulmonary-renal syndrome autologously induced anti-glomerular basement membrane disease in Wistar–Kyoto rats. Clin Exp Nephrol 14, 123–131 (2010). https://doi.org/10.1007/s10157-009-0260-9

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  • DOI: https://doi.org/10.1007/s10157-009-0260-9

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