Skip Navigation


NDT Advance Access originally published online on January 26, 2008
Nephrology Dialysis Transplantation 2008 23(7):2254-2259; doi:10.1093/ndt/gfm937
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
23/7/2254    most recent
gfm937v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Oda, T.
Right arrow Articles by Miura, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oda, T.
Right arrow Articles by Miura, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Elevated urinary plasmin activity resistant to {alpha}2-antiplasmin in acute poststreptococcal glomerulonephritis

Takashi Oda1, Kikuko Tamura2, Nobuyuki Yoshizawa3, Tetsuzo Sugisaki4, Koichi Matsumoto5, Motoshi Hattori6, Toshihiro Sawai7, Tamehachi Namikoshi1, Muneharu Yamada1, Yuichi Kikuchi1, Shigenobu Suzuki1 and Soichiro Miura1

1 Department of Internal Medicine, National Defense Medical College, Saitama, Japan 2 Department of Pediatrics, National Hospital Organization, Nishisaitama Chuo National Hospital, Saitama, Japan 3 Department of Medicine, Hirose Hospital, Saitama, Japan 4 Department of Nephrology, Showa University School of Medicine, Tokyo, Japan 5 Department of Nephrology, Nihon University School of Medicine, Tokyo, Japan 6 Department of Pediatric Nephrology, Tokyo Women's Medical College, Tokyo, Japan 7 Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan

Correspondence and offprint requests to: Takashi Oda, Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa-shi, Saitama 359-8513, Japan. Tel: +81-4-2995-1609; Fax: +81-4-2996-5201; E-mail: takashio{at}ndmc.ac.jp



   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 Supplementary data
 References
 
Background. A pathogenic role of intraglomerular plasmin bound to nephritogenic antigen (nephritis-associated plasmin receptor, NAPlr) and resistant to physiologic inhibitors such as {alpha}2-antiplasmin ({alpha}2-AP) has recently been proposed in acute poststreptococcal glomerulonephritis (APSGN). To confirm this concept, we analysed the urinary profile of plasmin cascade in APSGN patients.

Methods. Urine samples from 10 patients with APSGN, 12 patients with IgA nephropathy (IgAN), 10 patients with streptococcal infection without nephritis (SI) and 10 healthy control subjects were analysed. The {alpha}2-AP-resistant plasmin activity was assessed by a chromogenic assay after {alpha}2-AP was added to each urine sample. Urinary plasminogen activator (PA) and plasmin were further analysed by polyacrylamide gel zymography. Urinary NAPlr was assessed by western blot analysis in selected samples.

Results. Urinary {alpha}2-AP-resistant plasmin activity corrected for creatinine concentration (units/g · creatinine) was significantly higher in patients with APSGN (2.99 ± 0.63) than in patients with IgAN (1.02 ± 0.20, P < 0.01), SI (0.79 ± 0.17, P < 0.01), or in healthy control subjects (0.73 ± 0.18, P < 0.01). This tendency was confirmed by casein gel zymography. However urinary PA activity assessed by plasminogen–casein gel zymography did not differ between groups. NAPlr was detected in the urine of APSGN patients.

Conclusions. We found elevated urinary plasmin activity resistant to {alpha}2-AP, which may be due to urinary excretion of NAPlr in patients with APSGN. This result supports the pathogenic role of the NAPlr–plasmin complex in the development of APSGN. Furthermore, {alpha}2-AP-resistant urinary plasmin activity may be useful as a diagnostic marker for APSGN.

Keywords: acute poststeptococcal glomerulonephritis; {alpha}2-antiplasmin; nephritis-associated plasmin receptor; plasmin; zymography



   Introduction
Top
 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 Supplementary data
 References
 
Acute poststreptococcal glomerulonephritis (APSGN) is a sequela of streptococcal infection thought to be induced by a certain streptococcal antigen [1]. Identification of a causative antigen is critical for the elucidation of the mechanism of this disease; however, it remains a matter of debate [2–6]. Among known nephritogenic antigens, leading candidates include nephritis-associated plasmin receptor (NAPlr) [5,6] and streptococcal pyrogenic exotoxin B (SPEB) [3,4]. Despite the controversy regarding which is the principal antigen [7,8], NAPlr and SPEB share a common function. Both possess plasmin-binding capacity and may mediate glomerular damage via plasmin activity [3,9,10]. In general, the free form of plasmin is tightly regulated by physiologic inhibitors such as {alpha}2-antiplasmin ({alpha}2-AP) in vivo [11,12]. However, once plasmin binds to its receptor, it has been shown to be stabilized and resistant to physiologic inhibitors in vitro [11]. We reported involvement of such a mechanism in APSGN by showing prominent {alpha}2-AP-resistant glomerular plasmin activity in a distribution identical to that of NAPlr deposition in the renal biopsy tissues from APSGN patients [9]. Plasmin may degrade and injure a glomerular basement membrane via its proteolytic activity, but may also mediate inflammation by activating and accumulating monocytes and neutrophils in situ, thereby contributing to the formation of early glomerular lesions of APSGN.

NAPlr-bound plasmin should be stable and detectable in the urine of APSGN patients and may be a diagnostic marker. To confirm this, we evaluated urinary plasmin activity in patients with APSGN compared to that in patients with IgA nephropathy (IgAN), streptococcal infection without nephritis (SI) and in healthy individuals.



   Subjects and methods
Top
 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 Supplementary data
 References
 
Patients
Supernatants of freshly voided urine samples from 10 patients with APSGN, 12 patients with IgAN, 10 patients with SI and 10 healthy control subjects were used. Characteristics of APSGN, SI and IgAN patients are shown in Table 1. Although the mean age in each group varied (APSGN patients 17.50 ± 5.10, SI patients 14.10 ± 4.26, IgAN patients 23.83 ± 1.17 and healthy controls 26.80 ± 6.38), the difference was not significant between these four groups. In four APSGN patients (patients 1, 5, 8 and 10), urine samples were collected twice (at the early and the later time points after disease onset) with the interval of 12.00 ± 4.42 days, in order to evaluate the variation over time. APSGN was generally diagnosed on the basis of clinical and laboratory findings (onset as acute nephritic syndrome, urinalysis abnormality, ASO titre elevation, hypocomplementaemia and spontaneous complete recovery), but in two patients (patients 7 and 8) the final diagnosis was made by the characteristic histologic features of renal biopsy tissues to rule out progressive renal disease with acute nephritic syndrome (e.g. IgAN, lupus nephritis and rapidly progressive glomerulonephritis). Representative immunohistologic microphotographs of renal biopsy tissue of patient 7 are shown in a supplementary figure (available online). SI was diagnosed by the presence of upper respiratory symptoms with a positive test for group A streptococcal antigen (CLEARVIEW STREP A; Inverness Medical Japan Co., Chiba, Japan). We could confirm the ASO titre elevation in adult patients with SI, but we could not collect blood samples and could not assess the ASO titres in child patients with SI. IgAN was diagnosed histologically in all patients. Informed consent was obtained from each patient.


View this table:
[in this window]
[in a new window]

  		Table 1 Clinical and laboratory characteristics of APSGNa, SIb and IgANc patients

 
Chromogenic plasmin assay
Urinary plasmin activity was measured with a plasmin-specific substrate, Tos-Gly-Pro-Lys-p-nitroanilide (Chromozym PL; Roche Molecular Biochemicals, Indianapolis, IN, USA), essentially according to the manufacturer's instructions. In brief, 10 µl of 100 mIU/ml {alpha}2-AP (Merck, Darmstadt, Germany) and 50 µl urine sample were premixed in a 96-well plate, and buffer and chromogenic substrate solution were added to a final volume of 120 µl. An increase in absorbance at 405 nm after 2 h was calculated. Sample values were determined from standard curves generated with the use of serially diluted human plasmin (Wako Pure Chemical Industries, Osaka, Japan). Results were corrected for urinary creatinine concentration and expressed as units/g · creatinine (U/g · Cr). In addition, the inhibitory ability of {alpha}2-AP in our assay system was evaluated by comparing the chromogenic results of plasmin standards with or without addition of {alpha}2-AP (10 µl of 100 mIU/ml solution). Furthermore, in some urine samples (three IgAN patients and three healthy controls), chromogenic results with or without plasmin addition (5 ng of plasmin, which would correspond to the urinary plasmin activity level of 1.74 U/g · Cr at a urinary Cr concentration of 100 mg/dl) were compared to confirm the inhibitory efficacy of {alpha}2-AP against free plasmin.

Gel zymography for plasminogen activator (PA)/plasmin activity
PA and plasmin activities were assessed by polyacrylamide gel zymography as described previously [13]. Urine samples containing 2 µg and 40 µg creatinine were applied for plasminogen–casein and casein zymographic gels, respectively. Samples containing 40 µg creatinine were concentrated with centrifugal filter units (Ultrafree-MC; nominal molecular-weight limit: 10 kDa; Millipore, Bedford, MA, USA). Each sample was separated under non-reducing conditions on a 10% SDS–polyacrylamide gel containing 2 mg/ml casein (Sigma-Aldrich Co., St Louis, MO, USA) with or without 10 µg/ml plasminogen (Sigma-Aldrich). After being washed with 2.5% Triton X-100, gels were incubated in substrate buffer (0.1 M glycine, pH 8.3) at 37°C. The incubation time for plasminogen–casein gels was 12 h but that for casein gels was 36 h. Gels were then stained with 0.002% Coomassie blue. The density of each lytic band was quantified with image analysing software (CS Analyzer Version 2.0; ATTO, Tokyo, Japan). Linearization of the assay was ensured with the use of serially diluted human plasmin or low molecular weight (33 kDa) human urokinase-type plasminogen activator (uPA) (Calbiochem-Merck KgaA, Darmstadt, Germany) as a standard. To identify the band representing plasmin activity, adsorption tests were performed. Rabbit anti-human plasmin(ogen) antibody (Nordic Immunological Laboratories, Tilburg, The Netherlands) was immobilized with the use of a protein G immunoprecipitation kit (Seize X; Pierce, Rockford, IL, USA). Urine samples with or without immobilized antibody treatment were analysed by casein gel zymography.

Western blot analysis of NAPlr
The presence of NAPlr in urine was analysed by western blotting. We could analyse urine samples from all healthy controls and SI patients, and also from selected patients with APSGN (patients 1, 2, 3, 6 and 8) and IgAN (patients 3, 5, 6, 7, 9, 10 and 12), because of the limitation in the amount of collected urine sample for this study. Urine samples containing 40 µg creatinine (concentrated with Ultrafree-MC centrifugal filter units) were subjected to 10% SDS–PAGE, and proteins were transferred to a PVDF membrane. After being blocked with 5% skim milk in PBS containing 0.1% Tween 20 (PBS-T) for 1 h, the membrane was incubated with an anti-NAPlr antibody (5 µg/ml in 5% skim milk/PBS-T) for 1 h. The generation and the specificity of mouse anti-NAPlr monoclonal antibody (1F10) have recently been described [14]. After being washed in PBS-T, the membrane was incubated in peroxidase-conjugated goat anti-mouse IgG (Sigma-Aldrich) for 1 h, and reactive bands were detected with the ECL Plus detection kit (Amersham Biosciences, Piscataway, NJ, USA).

Statistical analysis
All values are expressed as mean ± standard error (SE). Generally, Student's t-test was used to evaluate differences in mean values between groups. However, in the assay of variation of urinary plasmin activity overtime, the Wilcoxon signed rank test was used. Differences were considered significant if the two-tailed P value was <0.05.



   Results
Top
 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 Supplementary data
 References
 
Chromogenic assay of plasmin activity
Compared to the strong positive linear regression of the chromogenic results by plasmin standards (Y = 0.001 + 0.02* X, r = 0.999, P < 0.0001), addition of {alpha}2-AP sufficiently inhibited the chromogenic reaction by plasmin standards up to the concentration level of 0.3 µg/ml (corresponding to the urinary plasmin activity level of 5.22 U/g · Cr at a urinary Cr concentration of 100 mg/dl) (Figure 1A). Moreover, the differences in the assay results between the crude urine samples and the samples with exogenous plasmin were minimal (1.26 ± 0.26 versus 1.35 ± 0.39), suggesting that {alpha}2-AP effectively inhibits the free plasmin in the present assay system. {alpha}2-AP-resistant urinary plasmin activity was significantly higher in APSGN patients (2.99 ± 0.63 U/g · Cr) than in IgAN patients (1.02 ± 0.20, P < 0.01), SI patients (0.79 ± 0.17, P < 0.01) or in healthy controls (0.73 ± 0.18, P < 0.01) (Figure 1B). Furthermore, in four APSGN patients from whom urine samples were collected twice in the disease course, the activity levels were always higher in the early collected samples than in the later collected samples (2.82 ± 1.08 versus 1.58 ± 0.86, P = 0.07) (Figure 1C).


Figure 1
View larger version (15K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 (A) Representative chromogenic results of plasmin standards. The plot of the {Delta}OD value by the chromogenic assay in relation to concentration of serially diluted human plasmin resulted in a positive linear regression. Addition of {alpha}2-antiplasmin ({alpha}2-AP) into plasmin standards sufficiently suppressed the {Delta}OD value by plasmin activity up to the concentration level of 0.3 µg/ml. (B) Urinary plasmin activity assessed by the chromogenic assay and corrected for urinary creatinine concentration. Supernatants of freshly voided urine samples from healthy control subjects; patients with streptococcal infection without nephritis (SI), patients with IgA nephropathy (IgAN) and patients with acute poststreptococcal glomerulonephritis (APSGN) were analysed. Results are expressed as corrected mean activity ± SE. *P < 0.01 versus healthy controls; {dagger}P < 0.01 versus SI; {ddagger}P < 0.01 versus IgAN. (C) Change of the urinary plasmin activity levels in the disease course of APSGN over time. Urine samples were collected twice (at the early timing after disease onset = early, later timing = late) in the disease course of APSGN patients (patients 1, 5, 8 and 10) and their plasmin activities were compared. Results are expressed as corrected mean activity ± SE.

 
Gel zymography profile of PA/plasmin activity
By casein gel zymography, several bands were detected in APSGN and IgAN patients but not in SI patients or in healthy controls, and the plasmin standard showed a doublet-triplet band at ~65–80 kDa (Figure 2A). Aprotinin treatment inhibited all bands similarly (data not shown), whereas adsorption of urine samples with anti-plasmin(ogen) antibody selectively inhibited the 80-kDa band (Figure 2B), suggesting that the band represents plasmin activity. Relative plasmin activity, as assessed by the density of the 80-kDa band, was similar to that determined by chromogenic assay (Figure 2C); activity was higher in APSGN patients (6.70 ± 3.14) than in controls (0 ± 0), SI patients (0 ± 0) or in IgAN patients (1.00 ± 0.55).


Figure 2
View larger version (25K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 (A) Representative casein gel zymography results of urine supernatants from healthy controls, patients with SI, patients with IgAN and patients with APSGN and of a plasmin standard (Plasmin). (B) Adsorption of the urine sample from an APSGN patient with immobilized anti-plasmin(ogen) antibody inhibited the 80-kDa band. (C) Graph shows density of 80-kDa bands in casein gel zymography expressed in arbitrary units as mean ± SE.

 
Two bands (33 and 54 kDa) representing low molecular weight and high molecular weight uPA were identified by plasminogen–casein gel zymography (Figure 3A); these bands were inhibited when amiloride (a uPA inhibitor) was added to the substrate buffer or in the absence of plasminogen (data not shown). Plasmin and tPA activities were not detected in plasminogen–casein zymographic gels under our assay conditions. Relative total PA activity, as assessed by the density sum of each band, was higher in APSGN patients (1.44 ± 0.25) than in IgAN patients (1.21 ± 0.12), SI patients (0.90 ± 0.22) or in healthy controls (1.00 ± 0.20), but differences between these four groups were not significant (Figure 3B).


Figure 3
View larger version (17K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 (A) Representative plasminogen–casein gel zymography results of urine supernatants from healthy control subjects, patients with SI, patients with IgAN and patients with APSGN. (B) Graph shows density sum of bands in plasminogen–casein gel zymography expressed in arbitrary units as mean ± SE.

 
Urinary NAPlr
Faint but distinct bands were detected at the predicted position of NAPlr (43 kDa) by western blot analysis of urine samples from some APSGN patients (three out of five patients analysed), but none in patients from other groups (Figure 4).


Figure 4
View larger version (36K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 4 Representative NAPlr western blot results of urine supernatants from healthy control subjects, patients with SI, patients with IgAN and patients with APSGN. The value on the left indicates the molecular weight of NAPlr.

 


   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
Supplementary data
 References
 
We recently found that the nephritogenic antigen for APSGN, which we termed NAPlr, was the same entity as plasmin receptor of group A streptococcus [5,6]. Furthermore, we showed that plasmin activity distributed identically with NAPlr in glomeruli of APSGN patients by in situ zymography (see supplementary figure, available online) [9]. These results indicate that glomerular bound NAPlr may bind to plasmin and maintain its proteolytic activity, thereby contributing to the development of APSGN in vivo. Because the NAPlr–plasmin complex is stable and protected from physiologic inhibitors, urinary plasmin activity in patients with APSGN is presumed to be elevated. To evaluate this, we first investigated urinary plasmin activity by a chromogenic assay. In the assay, {alpha}2-AP was added to urine samples to evaluate the fraction of plasmin activity resistant to {alpha}2-AP, which may reflect the amount of the NAPlr–plasmin complex and the APSGN condition. Preaddition of {alpha}2-AP would also eliminate the influence of free plasmin generated during assay incubation. As we expected, {alpha}2-AP-resistant plasmin activity was elevated in APSGN patients. However, several patients with IgAN also showed high plasmin activity. This may be due to the effect of non-plasmin urinary serine proteases that are resistant to {alpha}2-AP. The chromogenic substrate used in the plasmin assay (Tos-Gly-Pro-Lys-p-nitroanilide) has high affinity for and are sensitivity to plasmin, but it is not entirely specific; it is also sensitive to other serine proteases. Another possibility is that a certain proportion of IgAN cases were related to streptococcal infection. The possible contribution of chronic infection such as Haemophilus parainfluenzae [15] and Staphylococcus aureus [16] on IgAN has been reported. The important roles of streptococcal infection and glomerular NAPlr deposition have recently been demonstrated in more than a few HSPN patients [17]. The pathologic manifestations are similar in many aspects between HSPN and IgAN, so we do not think it a wild idea that some IgAN are induced by streptococcal infection similarly as HSPN. Indeed, there had been one report indicating the possible relationship between IgAN and streptococcal infection [18].

To rule out the influence of other urinary proteases, we further analysed plasmin activity by casein gel zymography. Gel zymography offers the molecular weight and is useful for the specific identification of plasmin activity. Results of casein gel zymography were similar to those of the chromogenic assay, but the difference between APSGN and IgAN patients was not significant (P = 0.07). This may due to differences in the sensitivity and specificity of these assays. The sensitivity of casein gel zymography is relatively poor (long incubation times and a urine concentrating step are necessary to obtain obvious bands). In addition, casein gel zymography may identify active plasmin (free or Plr-bound form) and also inactive plasmin bound to plasmin inhibitors such as {alpha}2-AP due to non-specific decomposition during SDS-PAGE.

Contrary to the results of casein gel zymography, plasminogen–casein gel zymography did not show significant differences between the four groups, confirming that significant elevation of urinary plasmin activity was not due to differences in PA activity. Although the difference was not significant, mean uPA activity was higher in APSGN. This may be due to the prominent glomerular infiltration of macrophages in APSGN [19]; macrophages are known to secrete uPA [20].

The concomitant existence of {alpha}2-AP-resistant plasmin activity and NAPlr in the urine of APSGN patients suggests that NAPlr and plasmin are excreted in the urine as a complex. Indeed, plasmin receptor (NAPlr) has been shown to bind to plasmin and maintain plasmin's proteolytic activity by protecting it from physiologic inhibitors in vitro [5,11]. Although no bands were detected at the expected size of the complex (~120 kDa), the NAPlr–plasmin complex was found to dissociate during SDS–PAGE in our preliminary experiments (data not shown).

Although the sample number analysed in the present study was too small to reach the definite conclusion, our results indicate that urinary plasmin activity may serve as a supportive diagnostic marker for APSGN. Differential diagnosis of severe APSGN from other renal diseases that manifest as acute nephritic syndrome, such as IgAN, rapidly progressive glomerulonephritis or lupus nephritis, is not always easy. Considering that the incidence of APSGN is higher in children and that the prognosis is generally good, avoiding invasive procedures such as renal biopsy is desirable. Not only as a diagnostic marker, the level of urinary plasmin activity may serve as a follow-up marker, because the level decreases rapidly over time reflecting the resolutional character of APSGN [19].

In summary, we identified elevation of urinary plasmin activity resistant to {alpha}2-AP and urinary excretion of NAPlr in patients with APSGN. The results support our concept that NAPlr-bound plasmin plays a role in the pathogenesis of APSGN and offers information regarding the development of diagnostic markers for APSGN.



   Supplementary data
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Supplementary data
References
 
Supplementary data is available online at http://ndt.oxfordjournals.org



   Acknowledgments
 
We are grateful to Ms Tatsuyo Harasawa, Central Research Laboratory, National Defense Medical College, for excellent technical assistance, and to Dr Kazuo Yamakami, Department of Preventive Medicine and Public Health, National Defense Medical College, for valuable advice and discussion. This work was supported by Kawano Masanori Memorial Foundation for Promotion of Pediatrics. A portion of this study was presented at the 38th ASN meeting on November 2005.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 Supplementary data
 References
 

  1. Silva FG. Acute postinfectious glomerulonephritis and glomerulonephritis complicating persistent bacterial infection. In: Heptinstall's Pathology of the Kidney—Jennette JC, Olson JL, Schwartz MM, Silva FG, eds. (1998) 1, 5th edn. Philadelphia: Lippincott-Raven. 389–453.
  2. Lange K, Seligson G, Cronin W. Evidence for the in situ origin of poststreptococcal glomerulonephritis: glomerular localization of endostreptosin and the clinical significance of the subsequent antibody response. Clin Nephrol (1983) 19:3–10.[Web of Science][Medline]
  3. Poon-King R, Bannan J, Viteri A, et al. Identification of an extracellular plasmin binding protein from nephritogenic streptococci. J Exp Med (1993) 178:759–763.[Abstract/Free Full Text]
  4. Cu GA, Mezzano S, Bannan JD, et al. Immunohistochemical and serological evidence for the role of streptococcal proteinase in acute post-streptococcal glomerulonephritis. Kidney Int (1998) 54:819–826.[CrossRef][Web of Science][Medline]
  5. Yamakami K, Yoshizawa N, Wakabayashi K, et al. The potential role for nephritis-associated plasmin receptor in acute poststreptococcal glomerulonephritis. Methods (2000) 21:185–197.[CrossRef][Web of Science][Medline]
  6. Yoshizawa N, Yamakami K, Fujino M, et al. Nephritis-associated plasmin receptor and acute poststreptococcal glomerulonephritis: characterization of the antigen and associated immune response. J Am Soc Nephrol (2004) 15:1785–1793.[Abstract/Free Full Text]
  7. Batsford SR, Mezzano S, Mihatsch M, et al. Is the nephritogenic antigen in post-streptococcal glomerulonephritis pyrogenic exotoxin B (SPEB) or GAPDH? Kidney Int (2005) 68:1120–1129.[CrossRef][Web of Science][Medline]
  8. Yoshizawa N, Yamakami K, Oda T. Nephritogenic antigen for acute poststreptococcal glomerulonephritis. Kidney Int (2006) 69:942–943.[Web of Science][Medline]
  9. Oda T, Yamakami K, Omasu F, et al. Glomerular plasmin-like activity in relation to nephritis-associated plasmin receptor in acute poststreptococcal glomerulonephritis. J Am Soc Nephrol (2005) 16:247–254.[Abstract/Free Full Text]
  10. Rodriguez-Iturbe B. Nephritis-associated streptococcal antigens: where are we now? J Am Soc Nephrol (2004) 15:1961–1962.[Free Full Text]
  11. D’Costa SS, Boyle MD. Interaction of group A streptococci with human plasmin(ogen) under physiological conditions. Methods (2000) 21:165–177.[CrossRef][Web of Science][Medline]
  12. Plow EF, Herren T, Redlitz A, et al. The cell biology of the plasminogen system. FASEB J (1995) 9:939–945.[Abstract]
  13. Oda T, Jung YO, Kim HS, et al. PAI-1 deficiency attenuates the fibrogenic response to ureteral obstruction. Kidney Int (2001) 60:587–596.[CrossRef][Web of Science][Medline]
  14. Fujino M, Yamakami K, Oda T, et al. Sequence and expression of NAPlr is conserved among group A streptococci isolated from patients with acute poststreptococcal glomerulonephritis (APSGN) and non-APSGN. J Nephrol (2007) 20:364–369.[Web of Science][Medline]
  15. Suzuki S, Nakatomi Y, Sato H, et al. Haemophilus parainfluenzae antigen and antibody in renal biopsy samples and serum of patients with IgA nephropathy. Lancet (1994) 343:12–16.[CrossRef][Web of Science][Medline]
  16. Koyama A, Sharmin S, Sakurai H, et al. Staphylococcus aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy. Kidney Int (2004) 66:121–132.[CrossRef][Web of Science][Medline]
  17. Masuda M, Nakanishi K, Yoshizawa N, et al. Group A streptococcal antigen in the glomeruli of children with Henoch-Schonlein nephritis. Am J Kidney Dis (2003) 41:366–370.[CrossRef][Web of Science][Medline]
  18. Rekola S, Bergstrand A, Bucht H, et al. Are beta-haemolytic streptococci involved in the pathogenesis of mesangial IgA-nephropathy? Proc Eur Dial Transplant Assoc Eur Ren Assoc (1985) 21:698–702.[Medline]
  19. Oda T, Yoshizawa N, Yamakami K, et al. Significance of glomerular cell apoptosis in the resolution of acute post-streptococcal glomerulonephritis. Nephrol Dial Transplant (2007) 22:740–748.[Abstract/Free Full Text]
  20. Vassalli JD, Dayer JM, Wohlwend A, et al. Concomitant secretion of prourokinase and of a plasminogen activator-specific inhibitor by cultured human monocytes-macrophages. J Exp Med (1984) 159:1653–1668.[Abstract/Free Full Text]
Received for publication: 13. 5.07
Accepted in revised form: 18.12.07


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?



This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
23/7/2254    most recent
gfm937v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Oda, T.
Right arrow Articles by Miura, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oda, T.
Right arrow Articles by Miura, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?