Identification of a unique glomerular factor X activator in murine lupus nephritis

Citation
S. Perampalam et al., Identification of a unique glomerular factor X activator in murine lupus nephritis, J AM S NEPH, 10(11), 1999, pp. 2332-2341
Citations number
48
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
ISSN journal
10466673 → ACNP
Volume
10
Issue
11
Year of publication
1999
Pages
2332 - 2341
Database
ISI
SICI code
1046-6673(199911)10:11<2332:IOAUGF>2.0.ZU;2-G
Abstract
The role of glomerular procoagulant activity (PCA) was studied in mice (MRL /lpr, NZBxWF(1), and BXSB) that are known to develop lupus nephritis. In yo ung mice (6 to 8 wk) without renal disease, there was no increase in sponta neous glomerular PCA. In contrast, order (5 to 8 mo) autoimmune mice had si gnificant augmentation in glomerular PCA, coinciding with the histologic ap pearance of severe glomerulonephritis and renal fibrin deposition. The PCA was characterized as a serine protease that directly activated factor X. Th is factor X activator is not tissue factor because (I) expression of PCA wa s not dependent on factor VII; (2) a monoclonal antibody against the factor X activator inhibited glomerular PCA, but not tissue factor; (3) the molec ular weight (66 kD) of the activator was different from that of tissue fact or; and (4) concanavalin A inhibited tissue factor but not glomerular PCA. Immunohistochemical studies localized the factor X activator to the glomeru lar mesangium and capillary wall of 4- to 6-mo-old diseased MRL/lpr mice. I mmunogold-labeled antibody bound to the dense deposits, macrophages, and en dothelial cells of diseased glomeruli. These studies define the role of a u nique glomerular factor X activator in murine lupus nephritis.