The participation of macrophages, glomerular procoagulant activity, and factor VIII in glomerular fibrin deposition. Studies on anti-GBM antibody-induced glomerulonephritis in rabbits.

ABSTRACT

The temporal relationships of macrophage accumulation, glomerular fibrin deposition, the expression of glomerular procoagulant activity (PCA), and Factor VIII antigen deposition were studied in rabbits in which antiglomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) developed. The initiation of injury coincided with the accumulation of glomerular macrophages. Glomerular fibrin, assessed by immunofluorescence and by deposition of 125I-fibrinogen, paralleled the development of glomerular crescents and renal impairment. Macrophage ingress clearly preceded the deposition of 125I-fibrinogen within glomeruli. Augmented levels of PCA were present in glomeruli prior to the initiation of fibrin deposition, and peak levels coincided with the peak glomerular macrophage presence. Factor VIII related antigen was apparent late in the disease and was present mainly at the margins of fibrinous crescents. These data demonstrate that accumulation of glomerular macrophages precedes glomerular fibrin deposition in anti-GBM GN. The augmentation of PCA, coincident with the appearance of glomerular macrophages, suggests a role for macrophage PCA in the initiation of fibrin deposition within the glomerular tuft in this model.