Artikel
Infiltration of immunocompetent cells and complement activation precede albuminuria in angiotensin II-induced renal damage
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Autoren
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E. Shagdarsuren
- Medical Faculty of the Charité, Franz Volhard Clinic HELIOS Klinikum-Berlin (Berlin, D)
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J. Braesen
- Medical Faculty of the Charité, Franz Volhard Clinic HELIOS Klinikum-Berlin (Berlin, D)
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M. Wellner
- Medical Faculty of the Charité, Franz Volhard Clinic HELIOS Klinikum-Berlin (Berlin, D)
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J. Park
- Department of Medicine-Nephrology, Hannover Medical School (Hannover, D)
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P. Gratzer
- Medical Faculty of the Charité, Franz Volhard Clinic HELIOS Klinikum-Berlin (Berlin, D)
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A. Fiebeler
- Department of Medicine-Nephrology, Hannover Medical School (Hannover, D)
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F.C. Luft
- Medical Faculty of the Charité, Franz Volhard Clinic HELIOS Klinikum-Berlin, Max Delbrück Centre for Molecular Medicine (Berlin, D)
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D. Müller
- Medical Faculty of the Charité, Franz Volhard Clinic HELIOS Klinikum-Berlin, Max Delbrück Centre for Molecular Medicine (Berlin, D)
| Veröffentlicht: | 10. August 2005 |
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Gliederung
Text
Objective: Albuminuria may induce tubulointerstitial infiltration of macrophages and lymphocytes, while interstitial nephritis may cause albuminuria. We investigated whether immunocompetent cell infiltration precedes or is the consequence of albuminuria in a model of Ang II-induced nephropathy.
Methods: We studied the time course of renal damage in double transgenic rats harboring both human renin and angiotensinogen genes (dTGR) from week 5 to week 7, with or without losartan (LOS) treatment. Non-transgenic Sprague-Dawley (SD) rats were controls.
Results: Systolic blood pressure was moderately increased at week 5 and peaked 210 mm Hg at week 7 in vehicle-treated dTGR. Albuminuria was not increased at week 5, increased slightly by week 6, and increased 150-fold at week 7, compared to (SD). Blood urea nitrogen and creatinine increased only at week 7. Elevated serum C-reactive protein, renal macrophage, T-cell, MHC II+, and CD86+ cell infiltration, as well as C1q, C3 and C5b-9 complement activation, occurred already at week 5 before the onset of albuminuria. Cell infiltration, albuminuria, complement activation, and glomerular IgG deposition increased over time and peaked at week 7. LOS treatment reduced albuminuria and all inflammatory processes significantly. We focused on the role of Ang II on complement activation in more detail. C1q was expressed in the vessel wall, while C3, active C3c, and C5b-9 immunostaining were observed in vessels, glomeruli, and tubules. We next asked whether or not Ang II induces C3 mRNA via a direct or indirect mechanism in vascular smooth muscle and tubular epithelial cells. TNF-Ą increased C3 mRNA by 10-fold and 30-fold respectively, while Ang II had no effect.
Conclusion: Our findings indicate that renal cell infiltration and complement activation occur before the development of albuminuria. Ang II initiates a cascade of events leading indirectly to complement activation through mediators such as TNF-Ą.
