Glomerular procoagulant activity in human proliferative glomerulonephritis

Abstract

Mechanisms for initiation of glomerular fibrin deposition were studied using renal tissue obtained from two patients with rapidly progressive, crescentic glomerulonephritis. Histological examination showed extensive glomerular monocyte infiltration and fibrin deposition in both patients. Sonicated cell suspensions of isolated glomeruli from these patients contained markedly augmented levels of procoagulant activity (PCA) compared with the levels found in normal glomeruli. This PCA was characterized as tissue factor by its functional dependence on Factors VII and V, independence of Factors VIII and XII, inhibition by concanavalin A and phospholipase C, and association with cell membranes. Its coagulant activity was also inhibited by a specific monoclonal anti-human tissue factor antibody. Tissue factor could be identified in glomeruli from these two patients by indirect immunofluorescence using this antibody. These studies implicate extrinsic pathway activation via tissue factor in intraglomerular deposition of fibrin in these patients. Activated monocytes, known to be a potent source of procoagulant activity and seen in large numbers within glomeruli from these patients, are a likely source of this tissue factor.