Human Pathology
Volume 41, Issue 9 , Pages 1276-1285, September 2010

Localization of nephritis-associated plasmin receptor in acute poststreptococcal glomerulonephritis

  • Takashi Oda, MD

      Affiliations

    • Department of Internal Medicine, National Defense Medical College, Saitama 359-8513, Japan
    • Corresponding Author InformationCorresponding author. Department of Internal Medicine, National Defense Medical College, Saitama 359-8513, Japan.
  • ,
  • Nobuyuki Yoshizawa, MD

      Affiliations

    • Hemodialysis Center, Chofu Hospital, Tokyo 182-0034, Japan
  • ,
  • Kazuo Yamakami, PhD

      Affiliations

    • Department of Preventive Medicine and Public Health, National Defense Medical College, Saitama 359-8513, Japan
  • ,
  • Kikuko Tamura, MD

      Affiliations

    • Department of Pediatrics, National Hospital Organization, Nishisaitama-Chuo National Hospital, Saitama 359-1151, Japan
  • ,
  • Aki Kuroki, MD

      Affiliations

    • Department of Nephrology, Showa University School of Medicine, Tokyo 142-8666, Japan
  • ,
  • Tetsuzo Sugisaki, MD

      Affiliations

    • Department of Nephrology, Showa University School of Medicine, Tokyo 142-8666, Japan
  • ,
  • Emi Sawanobori, MD

      Affiliations

    • Department of Pediatrics, Yamanashi Medical University, Yamanashi 409-3898, Japan
  • ,
  • Kohsuke Higashida, MD

      Affiliations

    • Department of Pediatrics, Yamanashi Medical University, Yamanashi 409-3898, Japan
  • ,
  • Yoshiyuki Ohtomo, MD

      Affiliations

    • Department of Pediatrics, Juntendo University Nerima Hospital, Tokyo 177-8521, Japan
  • ,
  • Osamu Hotta, MD

      Affiliations

    • Department of Nephrology, Sendai Shakaihoken Hospital, Miyagi 981-8501, Japan
  • ,
  • Hiroo Kumagai, MD

      Affiliations

    • Department of Internal Medicine, National Defense Medical College, Saitama 359-8513, Japan
  • ,
  • Soichiro Miura, MD

      Affiliations

    • Department of Internal Medicine, National Defense Medical College, Saitama 359-8513, Japan

Received 7 September 2009; received in revised form 16 February 2010; accepted 17 February 2010. published online 18 June 2010.

Summary 

The nephritis-associated plasmin receptor is a recently identified nephritogenic antigen associated with acute poststreptococcal glomerulonephritis and proposed to play a pathogenic role, but its precise glomerular localization in acute poststreptococcal glomerulonephritis has not been elucidated. We therefore analyzed renal biopsy sections from 10 acute poststreptococcal glomerulonephritis patients by using immunofluorescence staining with anti–nephritis-associated plasmin receptor antibody and various markers of glomerular components. Nephritis-associated plasmin receptor was detected in the glomeruli of all patients, and double staining for nephritis-associated plasmin receptor and collagen IV showed nephritis-associated plasmin receptor to be predominantly on the inner side of the glomerular tufts. Nephritis-associated plasmin receptor–positive areas within glomerular tufts were further characterized with markers for neutrophils, mesangial cells, endothelial cells, and macrophages. In 6 of the patients, nephritis-associated plasmin receptor staining was seen mainly in neutrophils and to a lesser degree in mesangial and endothelial cells. In the other 4 patients, nephritis-associated plasmin receptor staining was seen mainly in mesangial cells and to a lesser degree in neutrophils and endothelial cells. In all patients, macrophages showed little staining. Elevated plasmin activity in glomerular neutrophils was identified by combining in situ zymography staining for plasmin activity and immunofluorescence staining for neutrophils. The glomerular localizations of nephritis-associated plasmin receptor and another nephritogenic antigen, streptococcal pyrogenic exotoxin B, were compared by double immunofluorescence staining and found to be similar. These findings indicate the nephritogenic potential of nephritis-associated plasmin receptor and offer valuable information with respect to the pathogenic mechanism of acute poststreptococcal glomerulonephritis.

Keywords: Acute poststreptococcal glomerulonephritis, Nephritis-associated plasmin receptor, Neutrophil, Plasmin, Streptococcal pyrogenic exotoxin B

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PII: S0046-8177(10)00084-5

doi:10.1016/j.humpath.2010.02.006

Human Pathology
Volume 41, Issue 9 , Pages 1276-1285, September 2010