Cell Biology – Immunology – Pathology
Kidney International (2001) 59, 1762–1769; doi:10.1046/j.1523-1755.2001.0590051762.x
Monocyte chemoattractant protein-1 and osteopontin differentially regulate monocytes recruitment in experimental glomerulonephritis
Ulf Panzer, Friedrich Thaiss, Gunther Zahner, Petra Barth, Mariola Reszka, Rolf R Reinking, Gunter Wolf, Udo Helmchen and Rolf A K Stahl
Department of Medicine, Division of Nephrology and Department of Pathology, University of Hamburg, Hamburg, Germany
Correspondence: Rolf A.K. Stahl, M.D., Division of Nephrology, Department of Medicine, University of Hamburg, Pav 61, Martinistra
e 52, 20246 Hamburg, Germany. E-mail: rstahl@uke.uni-hamburg.de
Received 8 June 2000; Revised 8 November 2000; Accepted 20 November 2000.
Abstract
Monocyte chemoattractant protein-1 and osteopontin differentially regulate monocytes recruitment in experimental glomerulonephritis.
Background
This study evaluated the mechanisms of monocyte/macrophage (M/M) infiltration in a rat model of anti-glomerular basement membrane glomerulonephritis (GN). We focused on chemokines and osteopontin, which are known regulators of M/M recruitment.
Methods
Using immunohistology, in situ hybridization, and Northern blotting, the expression levels of chemokines and osteopontin were evaluated in isolated glomeruli and tubules 4, 10, and 20 days after the induction of GN. In vivo blocking experiments were performed by application of neutralizing antibodies against osteopontin and monocyte chemoattractant protein-1 (MCP-1).
Results
In nephritic animals, high glomerular MCP-1 and RANTES (regulated upon activation normal T cell expressed and secreted) expression levels were observed on days 4 and 10. The tubular expression of MCP-1, however, was only slightly enhanced. In contrast, tubular osteopontin production was maximally stimulated (day 10) and paralleled with peaks of albuminuria and tubulointerstitial M/M infiltration. Application of an anti-osteopontin antibody ameliorated tubulointerstitial and glomerular M/M recruitment, whereas treatment with an anti–MCP-1 antibody selectively reduced glomerular M/M recruitment. However, tubulointerstitial M/M infiltration remained unchanged.
Conclusion
These studies show that chemokines and osteopontin are differentially expressed in glomeruli and tubules in this model of GN. Chemokines play a primary role in the glomeruli, whereas osteopontin has a predominant role in tubulointerstitial M/M recruitment. The roles of chemokines and osteopontin may thus be dependent on the renal compartment and on the disease model.
Keywords:
glomerular monocytes, tubulointerstitial monocytes, macrophages, mononuclear cells, progressive renal disease, inflammatory cell recruitment
