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

X. Q. Yu, D. J. Nikolic-Paterson, W. Mu, C. M. Giachelli, R. C. Atkins, R. J. Johnson, H. Y. Lan

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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.

Original languageEnglish
Title of host publicationProceedings of the Association of American Physicians
Place of PublicationUnited States
PublisherWiley-Blackwell
Pages50-64
Number of pages15
Volume110
Edition1
Publication statusPublished - 6 Feb 1998
Externally publishedYes

Keywords

  • CD44
  • ICAM-1
  • Macrophage
  • Renal injury
  • T cell

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