Identification of a Unique Glomerular Factor X Activator in Murine Lupus Nephritis Academic Article uri icon

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abstract

  • Abstract. The role of glomerular procoagulant activity (PCA) was studied in mice (MRL/lpr, NZBxWF1, and BXSB) that are known to develop lupus nephritis. In young mice (6 to 8 wk) without renal disease, there was no increase in spontaneous glomerular PCA. In contrast, older (5 to 8 mo) autoimmune mice had significant augmentation in glomerular PCA, coinciding with the histologic appearance of severe glomerulonephritis and renal fibrin deposition. The PCA was characterized as a serine protease that directly activated factor X. This factor X activator is not tissue factor because (1) expression of PCA was not dependent on factor VII; (2) a monoclonal antibody against the factor X activator inhibited glomerular PCA, but not tissue factor; (3) the molecular weight (66 kD) of the activator was different from that of tissue factor; and (4) concanavalin A inhibited tissue factor but not glomerular PCA. Immunohistochemical studies localized the factor X activator to the glomerular mesangium and capillary wall of 4- to 6-moold diseased MRL/lpr mice. Immunogold-labeled antibody bound to the dense deposits, macrophages, and endothelial cells of diseased glomeruli. These studies define the role of a unique glomerular factor X activator in murine lupus nephritis.

authors

  • PERAMPALAM, SUBODINI
  • WANG, LUOQUAN
  • MYERS-MASON, NANCY
  • YEOW, JEN NEI
  • STANIETSKY, NIR
  • PHILLIPS, JAMES
  • Weitz, Jeffrey
  • ACKERLEY, CAMERON
  • LEVY, GARY A
  • COLE, EDWARD H

publication date

  • November 1999