A functional role for osteopontin in experimental crescentic glomerulonephritis in the rat

Proc Assoc Am Physicians. Jan-Feb 1998;110(1):50-64.

Abstract

This study examined whether osteopontin (OPN), a molecule with monocyte chemotactic and adhesive activity, participates in macrophage-mediated renal disease, Accelerated anti-glomerular basement membrane glomerulonephritis was induced in groups of six rats. Animals were treated with a neutralizing anti-OPN or an irrelevant control antibody over days 0-7 (induction phase) or days 7-14 (established disease). Administration of the control antibody had no effect on the severity of the disease. In contrast, anti-OPN treatment significantly reduced glomerular injury (urinary protein excretion) and prevented a loss of renal function (creatinine clearance) during the induction of disease. This was accompanied by a significant reduction in renal macrophage and T-cell accumulation, T-cell activation, and histological injury (glomerular hypercellularity, segmental lesions, crescents, and tubulointerstitial lesions). An important finding was that anti-OPN treatment of established crescentic glomerulonephritis led to a significant reduction in glomerular injury and recovery of renal function in association with inhibition of macrophage and T-cell accumulation, T-cell activation, and histological damage. Anti-OPN treatment significantly inhibited the upregulation of OPN and its ligand CD44 but demonstrated no effect on upregulation of intercellular adhesion molecule-1 (ICAM-1) expression in the kidney. Interestingly, anti-OPN treatment significantly reduced skin swelling and leukocyte infiltration in the delayed type hypersensitivity response. However, anti-OPN treatment had no effect on the humoral immune response. In summary, this study has demonstrated that OPN plays a functional role in macrophage and T-cell accumulation and renal damage in both the induction and progression of a rat model of crescentic glomerulonephritis. Thus, OPN may be of pathological importance in human glomerulonephritis and in cell-mediated immune diseases generally.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Glomerulonephritis / immunology*
  • Glomerulonephritis / pathology
  • Glomerulonephritis / physiopathology
  • Humans
  • Hyaluronan Receptors / biosynthesis
  • Hypersensitivity, Delayed
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Kidney / physiopathology
  • Leukocytes / cytology
  • Male
  • Osteopontin
  • Rats
  • Rats, Sprague-Dawley
  • Sialoglycoproteins / biosynthesis
  • Sialoglycoproteins / immunology*
  • Skin / immunology

Substances

  • Hyaluronan Receptors
  • SPP1 protein, human
  • Sialoglycoproteins
  • Spp1 protein, rat
  • Osteopontin
  • Intercellular Adhesion Molecule-1