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Identification of a Unique Glomerular Factor X Activator in Murine Lupus Nephritis

SUBODINI PERAMPALAM^*, LUOQUAN WANG, NANCY MYERS-MASON, JEN NEI YEOW^*, NIR STANIETSKY, JAMES PHILLIPS, JEFFREY I. WEITZ^§, CAMERON ACKERLEY, GARY A. LEVY^*, and EDWARD H. COLE

^* Department of Pathology, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada
Department of Medicine, The Toronto Hospital, University of Toronto, Toronto, Ontario, Canada
Department of Pathology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
^§ Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Correspondence to Dr. Edward H. Cole, The Toronto Hospital, General Division, 621 University Avenue, NU 10-158, Toronto, Ontario, Canada M5G 2C4. Phone: 416-340-4669; Fax: 416-340-3492; E-mail: ecole{at}torhosp.toronto.on.ca

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.

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673