Original Paper

Role of Thrombospondin-1 in the Autologous Phase of an Accelerated Model of Anti-Glomerular Basement Membrane Glomerulonephritis
Kathrin Hochegger^a, Sara Knight^b, Christian Hugo^c, Gert Mayer^a, Jack Lawler^d, Tanya N. Mayadas^b, Alexander R. Rosenkranz<sup>a

a</sup>Klinische Abteilung für Nephrologie, Universitätsklinik für Innere Medizin Innsbruck, Innsbruck, Austria;
^bDepartment of Pathology, Brigham and Women`s Hospital, Harvard Medical School, Boston, Mass., USA;
^cAbteilung für Nephrologie, Universität Erlangen-Nürnberg, Erlangen, Germany;
^dDepartment of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass., USA

Address of Corresponding Author

Nephron Exp Nephrol 2004;96:e31-e38 (DOI: 10.1159/000076402)

  Key Words

• Thrombospondin-1
• Transgenic mice
• Glomerulonephritis

  Abstract

Background: Thrombospondin-1 (TSP1), a multifunctional, extracellular matrix protein, regulates cellular attachment, proliferation, migration, and differentiation in vitro, and is expressed de novo in many inflammatory diseases, including glomerulonephritis (GN). Methods: We investigated the role of TSP1 in the autologous phase of an accelerated model of anti-glomerular basement membrane (GBM) GN in mice deficient in TSP1. The model, induced by the injection of rabbit anti-mouse GBM antibody, is characterized by the development of proteinuria and glomerular damage over a 21-day observation period in wild-type mice. Results: Mice deficient in TSP1 developed significantly less proteinuria than their wild-type controls 21 days after induction of disease (5,793 ± 5,456 vs. 24,293 ± 15,336 µg albumin/mg creatinine; p = 0.002). Serum creatinine levels were significantly higher in the wild-type mice than in the TSP1 deficient animals (29.03 ± 2.34 vs. 16.39 ± 2.87 µmol/l; p = 0.005). Other disease indices as crescent formation, fibrin deposition and macrophage influx, were also diminished in the TSP1 knockout animals. The numbers of interstitial CD4+ and CD8+ T cells were generally less in TSP1-deficient mice and reached statistical significance in CD4+ (p = 0.01) and CD8+ T cells (p = 0.02). The difference in outcome of the disease was not due to the difference in deposition/production of heterologous and autologous antibodies in the two groups of animals. Conclusion: This study suggests a proinflammatory role of TSP1 in an experimental model of GN.

Copyright © 2004 S. Karger AG, Basel

  Author Contacts

Dr. Alexander Rosenkranz
Klinische Abteilung für Nephrologie, Universitätsklinik für Innere Medizin
Anichstrasse 35
AT-6020 Innsbruck (Austria)
Tel. +43 512 504 5855 or 3387, E-Mail alexander.rosenkranz@uibk.ac.at

  Article Information

Received: May 7, 2003
Accepted: September 23, 2003
Number of Print Pages : 8
Number of Figures : 5, Number of Tables : 1, Number of References : 32