Identification of a unique glomerular factor X activator in murine lupus nephritis.
The role of glomerular procoagulant activity (PCA) was studied in mice (MRL/lpr, NZBxWF,, 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-mo-old 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.
Perampalam
S
S
Department of Pathology, The Toronto Hospital, Ontario, Canada.
Wang
L
L
Myers-Mason
N
N
Yeow
J N
JN
Stanietzky
N
N
Phillips
J
J
Weitz
J I
JI
Ackerley
C
C
Levy
G A
GA
Cole
E H
EH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015153:Blotting, Western; D003546:Cysteine Endopeptidases / Q000032:analysis* / Q000502:physiology; D005170:Factor X / Q000378:metabolism; D005260:Female; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000648:ultrastructure; D008181:Lupus Nephritis / Q000209:etiology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D008856:Microscopy, Fluorescence; D009363:Neoplasm Proteins; D011516:Prothrombin / Q000378:metabolism; D013925:Thromboplastin / Q000032:analysis
D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; D011516:Prothrombin; D005170:Factor X; D013925:Thromboplastin; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant