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.