title: Quantitation and characterization of glomerular procoagulant activity in experimental glomerulonephritis.
abstract: Glomerular procoagulant activity (PCA) was studied in four different models of experimental glomerulonephritis (GN) in rabbits. These models included 3 macrophage-dependent models: active autologous phase anti-glomerular basement membrane (GBM) antibody induced GN (active anti-GBMGN); passively induced autologous phase anti-GBMGN, and acute serum sickness; and a macrophage independent model of injury, heterologous phase anti-GBMGN was included also. PCA in glomerular lysates was significantly augmented in the three macrophage-dependent models, but not elevated significantly in heterologous anti-GBMGN when compared to glomerular lysates from normal rabbits. The greatest augmentation of PCA was found in glomeruli from rabbits with active anti-GBMGN which also contained the greatest numbers of macrophages. The functional characteristics of the glomerular PCA were similar in each of the models studied. Initiation of coagulation in vitro by these lysates was shown to be dependent on the presence of coagulation Factors VII and V, and largely independent of Factors XII and VIII, suggesting that glomerular PCA activates the extrinsic coagulation pathway. Inhibition studies using concanavalin A and phospholipase C demonstrated that glycoside residues and phospholipids are important chemical moieties for the coagulant activity of PCA. After sonication and ultracentrifugation PCA was found in the cell membrane fraction but not in the cell cytosol of glomerular lysates. These studies provide further evidence that glomerular PCA is markedly augmented in the presence of infiltrating glomerular macrophages and demonstrate that glomerular PCA has the functional characteristics of 'tissue factor', the procoagulant expressed by macrophages on their cell surface membrane. The quantitative association of glomerular PCA with glomerular macrophages, together with the shared functional characteristics of glomerular PCA and macrophage PCA, together suggests that the augmented glomerular PCA in experimental GN is due to tissue factor from infiltrating macrophages (macrophage PCA).
mesh_terms: D000818:Animals; D001779:Blood Coagulation Factors / Q000032:analysis*; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000503:physiopathology*; D007106:Immune Sera; D007678:Kidney Glomerulus / Q000503:physiopathology*; D008264:Macrophages / Q000502:physiology*; D011817:Rabbits; D012713:Serum Sickness / Q000503:physiopathology
chemical_list: D001779:Blood Coagulation Factors; D007106:Immune Sera; C045072:macrophage procoagulant activity