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Streptococcal zymogen type B induces angiotensin II in mesangial cells and leukocytes

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Abstract

Previous reports have shown that angiotensin II and oxidative stress may be important features in acute poststreptococcal glomerulonephritis (APSGN) and that streptococcal erythrogenic toxin type B (ETB) and its precursor (ETBP) may have an important role in the pathogenesis of APSGN. The aim of this study was to determine the effect of ETBP on the production of angiotensin II and oxidative stress in rat mesangial cells and human mononuclear leukocytes. Mesangial cells and leukocytes were isolated from digested glomeruli and by histopaque gradient, respectively, while ETBP was isolated from nephritogenic streptococcus cultures using a cation exchange column. Angiotensin II was determined by an enzyme-linked immunosorbent assay and by cytometrics. Superoxide anion, reduced glutathione, nitrites, lipid peroxidation and catalase activity were determined by cytochemical, biochemical and enzymatic assays. Inducible nitric oxide synthase expression was determined by cytometrics. An increased production of angiotensin II was observed in ETBP-treated mesangial cell and leukocyte cultures. The ETBP induced an elevated production of superoxide anions and nitrites in mesangial cells and superoxide anions in leukocytes, while this streptococcal protein decreased the expression of inducible nitric oxide synthase in leukocytes. The ETBP was capable of inducing an increased production of angiotensin II and increased oxidative stress, both of which may be important mediators of inflammatory events in the renal tissue and during APSGN.

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References

  1. Vogt A, Batsford S, Rodriguez-Iturbe B, Garcia R (1983) Cationic antigens in poststreptococcal glomerulonephritis. Clin Nephrol 20:271–279

    CAS  PubMed  Google Scholar 

  2. Cu GA, Mezzano S, Bannan JD, Zabriskie JB (1998) Immunohistochemical and serological evidence for the role of streptococcal proteinase in acute post-streptococcal glomerulonephritis. Kidney Int 54:819–826

    Article  CAS  Google Scholar 

  3. Batsford SR, Mezzano S, Mihatsch M, Schiltz E, Rodríguez-Iturbe B (2006) Is the nephritogenic antigen in post-streptococcal glomerulonephritis pyrogenic exotoxin B (SPE B) or GAPDH? Kidney Int 68:1120–1129

    Article  Google Scholar 

  4. Parra G, Rodriguez-Iturbe B, Batsford S, Vogt A, Mezzano S, Olavarria F, Exeni R, Laso M, Orta N (1998) Antibody to streptococcal zymogen in the serum of patients with acute glomerulonephritis: a multicentric study. Kidney Int 54:509–517

    Article  CAS  Google Scholar 

  5. Viera NT, Romero MJ, Montero MK, Rincon J, Mosquera JA (2001) Streptococcal erythrogenic toxin B induces apoptosis and proliferation in human leukocytes. Kidney Int 59:950–958

    Article  CAS  Google Scholar 

  6. Rincon J, Viera NT, Romero MJ, Mosquera JA (2003) Increased production of chemotactic cytokines and elevated proliferation and expression of intercellular adhesion molecule-1 in rat mesangial cells treated with erythrogenic toxin type b and its precursor isolated from nephritogenic streptococci. Nephrol Dial Transplant 18:1072–1078

    Article  CAS  Google Scholar 

  7. Pedreanez A, Viera N, Rincon J, Mosquera J (2006) Increased IL-6 in supernatant of rat mesangial cell cultures treated with erythogenic toxin type b and its precursor isolated from nephritogenic streptococci. Am J Nephrol 26:75–81

    Article  CAS  Google Scholar 

  8. Viera N, Pedreanez A, Rincon J, Mosquera J (2007) Streptococcal exotoxin B increases interleukin-6, tumor necrosis factor alpha, interleukin-8 and transforming growth factor beta-1 in leukocytes. Pediatr Nephrol 22:1273–1281

    Article  Google Scholar 

  9. Yamamoto T, Nakagawa T, Suzuki H, Ohashi N, Fukasawa H, Fujigaki Y (2007) Urinary angiotensinogen as a marker of intrarenal angiotensin II activity associated with deterioration of renal function in patients with chronic kidney disease. J Am Soc Nephrol 18:1558–1565

    Article  CAS  Google Scholar 

  10. Yoon JM, Pahl MV, Vaziri ND (2007) Spontaneous leukocyte activation and oxygen-free radical generation in end-stage renal disease. Kidney Int 71:167–172

    Article  CAS  Google Scholar 

  11. Morsi MR, Madina EH, Anglo AA, Soliman AT (1992) Evaluation of captopril versus reserpine and frusemide in treating hypertensive children with acute post-streptococcal glomerulonephritis. Acta Paediatr 81:145–149

    Article  CAS  Google Scholar 

  12. Parra G, Rodríguez-Iturbe B, Colina-Chourio J, García R (1988) Short-term treatment with captopril in hypertension due to acute glomerulonephritis. Clin Nephrol 29:58–62

    CAS  PubMed  Google Scholar 

  13. Kikuchi Y, Yoshizawa N, Oda T, Imakiire T, Suzuki S, Miura S (2006) Streptococcal origin of a case of Henoch-Schoenlein purpura nephritis. Clin Nephrol 65:124–128

    Article  CAS  Google Scholar 

  14. Devasena T, Lalitha S, Padma K (2001) Lipid peroxidation, osmotic fragility and antioxidant status in children with acute post-streptococcal glomerulonephritis. Clin Chim Acta 308:155–161

    Article  CAS  Google Scholar 

  15. Briggs RT, Robinson JM, Karnovsky ML, Karnovsky MJ (1986) Superoxide production by polymorphonuclear leukocytes. Histochemistry 84:371–378

    Article  CAS  Google Scholar 

  16. Archer S (1993) Measurement of nitric oxide in biological models. FASEB J 7:349–359

    Article  CAS  Google Scholar 

  17. Aebi HE (1982) Catalase. In: Bergmeyer HU (ed) Methods of enzymatic analysis, 3rd edn. Verlag Chemie, Deerfield Beach, pp 271–282

  18. Beutler E, Duron O, Milkus B (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 16:882–888

    Google Scholar 

  19. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  Google Scholar 

  20. Dietze GJ, Henriksen EJ (2008) Angiotensin-converting enzyme in skeletal muscle: sentinel of blood pressure control and glucose homeostasis. J Renin Angiotensin Aldosterone Syst 9:75–88

    Article  CAS  Google Scholar 

  21. Ruiz-Ortega M, Lorenzo O, Rupérez M, Esteban V, Suzuki Y, Mezzano S, Plaza JJ, Egido J (2001) Role of renin-angiotensin system in vascular diseases. Hypertension 38:1382–1387

    Article  CAS  Google Scholar 

  22. Ruiz-Ortega M, Lorenzo O, Ruperez M, Konig S, Wittig B, Egido J (2000) Angiotensin II actives nuclear transcription factor kB through AT 1 and AT2 in vascular smooth muscle cells: molecular mechanisms. Circulation Res 86:1266–1272

    Article  CAS  Google Scholar 

  23. Turi S, Nemeth I, Torkos A, Saghy L, Varga I, Matkovics B, Nagy J (1997) Oxidative stress and antioxidant defense mechanism in glomerular diseases. Free Radic Biol Med 22:161–168

    Article  CAS  Google Scholar 

  24. Tian J, Chen JH, Li Q, He Q, Lin WQ (2005) Lipid peroxidation in IgA nephropathy and the effect of lipo-prostaglandin E1. J Nephrol 18:243–248

    CAS  PubMed  Google Scholar 

  25. Pueyo ME, Gonzalez W, Nicoletti A, Savoie F, Arnal JF, Michel JB (2000) Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor–kB activation induced by intracellular oxidative stress. Arterioscler Thromb Vasc Biol 20:645–651

    Article  CAS  Google Scholar 

  26. Didion SP, Faraci FM (2003) Angiotensin II produces superoxide-mediated impairment of endothelial function in cerebral arterioles. Stroke 34:2038–2042

    Article  CAS  Google Scholar 

  27. Pedreanez A, Arcaya JL, Carrizo E, Mosquera J (2006) Forced swimming test increases superoxide anion positive cells and angiotensin II positive cells in the cerebrum and cerebellum of the rat. Brain Res Bull 71:18–22

    Article  CAS  Google Scholar 

  28. Zimmerman MC, Lazartigues E, Sharma RV, Davisson RL (2004) Hypertension caused by angiotensin II infusion involves increased superoxide production in the central nervous system. Circulation Res 95:210–217

    Article  CAS  Google Scholar 

  29. Erdos B, Broxson CS, King MA, Scarpace PJ, Tumer N (2006) Acute pressor effect of central angiotensin II is mediated by NAD(P)H-oxidase-dependent production of superoxide in the hypothalamic cardiovascular regulatory nuclei. J Hypertens 24:109–116

    Article  Google Scholar 

  30. Nickenig G, Harrison DG (2002) The AT1-type angiotensin receptor in oxidative stress and atherosclerosis, part I: oxidative stress and atherogenesis. Circulation 105:393–396

    Article  CAS  Google Scholar 

  31. Fux CA, Bianchetti MG, Jakob SM, Remonda L (2006) Reversible encephalopathy complicating post-streptococcal glomerulonephritis. Pediatr Infect Dis J 25:85–87

    Article  Google Scholar 

  32. Ritt M, Campean V, Amann K, Heider A, Griesbach D, Veelken R (2006) Transient encephalopathy complicating poststreptococcal glomerulonephritis in an adult with diagnostic findings consistent with cerebral vasculitis. Am J Kidney Dis 48:489–494

    Article  Google Scholar 

  33. Aeby A, David P, Fricx C, Jissendi P, Blecic S, Van Bogaert P (2006) Posterior reversible encephalopathy syndrome revealing acute post-streptococcal glomerulonephritis. J Child Neurol 21:250–251

    PubMed  Google Scholar 

  34. Vosti KL, Lindberg LH, Kosek JC, Raffel S (1970) Experimental streptococcal glomerulonephritis: Longitudinal study of a laboratory model resembling human acute poststreptococcal glomerulonephritis. J Infect Dis 122:249–259

    Article  CAS  Google Scholar 

  35. Okada K, Hirota K, Zhang RJ, Yasutoma K, Kuhara T, Ota F, Kagami S, Kuroda Y (1995) Possible role for a polysaccharide antigen shared between Streptococcus pyogenes and S. mutants in the pathogenesis of poststreptococcal glomerulonephritis. Acta Paediatr Jpn 38:470–475

    Google Scholar 

  36. Luo Y-H, Kuo C-F, Huang K-J, Wu J-J, Lei H-Y, Lin MT, Chuang W-J, Liu C-C, Lin C-F, Lin Y-S (2007) Streptococcal pyrogenic exotoxin B antibodies in a mouse model of glomerulonephritis. Kidney Int 72:716–724

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This manuscript was supported by CONDES (VAC-CONDES-CC-0763-06). The authors thank Dr. Arnold Vogt and Stephen Batsford for their generous gift of ETBP.

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Authors and Affiliations

  1. Instituto de Investigaciones Odontologicas, Facultad de Odontología, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela

    Ninoska Viera

  2. Catedra de Inmunologia, Escuela de Bioanalisis, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela

    Adriana Pedreanez

  3. Instituto de Investigaciones Clinicas Dr. Americo Negrette, Facultad de Medicina, Universidad del Zulia, Maracaibo, Venezuela

    Jaimar Rincon & Jesus Mosquera

  4. Apartado Postal 23, 4001-A, Maracaibo, Zulia, Venezuela

    Jesus Mosquera

Authors
  1. Ninoska Viera
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  2. Adriana Pedreanez
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  3. Jaimar Rincon
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  4. Jesus Mosquera
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Correspondence to Jesus Mosquera.

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Viera, N., Pedreanez, A., Rincon, J. et al. Streptococcal zymogen type B induces angiotensin II in mesangial cells and leukocytes. Pediatr Nephrol 24, 1005–1011 (2009). https://doi.org/10.1007/s00467-008-1105-6

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  • DOI: https://doi.org/10.1007/s00467-008-1105-6

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