Intraglomerular Deposition of Coagulation-Fibrinolysis Factors and a Platelet Membrane Antigen in Various Glomerular Diseases

Abstract

The intraglomerular location of coagulation-fibrinolysis factors (CFF) and a platelet membrane antigen (glycoprotein IIb-IIIa; GPIIb-IIIa) was determined in 101 patients with various glomerular diseases. Renal biopsy specimens were examined by immunofluorescence microscopy, using antisera against fibrinogen/fibrin reactive antigen (FRA), cross-linked fibrin degradation products (XL-FDP), fibronectin (FN), factor XIH-subunit a (F-XIIIa), plasminogen (Pig), α₂-plasmin inhibitor (α₂-PI) and GPIIb-IIIa. Intraglomerular deposits of the CFF were found at high rates in patients with IgA glomerulonephritis (GN), membranous nephropathy (MN) and lupus GN. The coexistence of deposits of these factors was ascertained by the double-staining method. The deposition rates of XL-FDP and GPIIb-IIIa were very low in patients with minimal-change nephrotic syndrome and focal glomerulosclerosis. Some cases of diabetic glomerulosclerosis (DGS) showed CFF deposition. FRA deposits associated with F-XIIIa and FN may indicate the presence of the cross-linked fibrin. Furthermore, the presence of Pig deposits together with α₂-PI and XL-FDP suggests the deposition of fibrin followed by fibrinolysis, but not of fibrinogen, and the coexistence of GPIIb-IIIa suggests the involvement of platelets in the reactions. These studies provide evidence that stabilized fibrin deposition with subsequent fibrinolysis and platelet activation take place in glomeruli in a fairly large proportion of patients with IgA GN, MN and lupus GN and in some cases of DGS.

Immunoelectron Microscopic Localization of Fibronectin and Complement to ‘Dense Bodies’ in Bowman’s Capsule and the Glomerular Basement Membrane in Membranous Nephropathy

“…Polymorphs, macrophages, monocytes and lymphocytes all have receptors for C3b [4]. The action of complement is enhanced by fibronectin and it initiates Fc and C3 receptor cell-mediated phagocytosis [5], The membrane attack complex and coagulation-fi brinolysis factors have previously been detected in the GBM and BC by immunofluorescence microscopy in membranous nephropathy [6][7][8]. Another study suggests that the immune deposits seen in stage 3 membranous nephropathy themselves trigger the C5b-9 complement sequence [9].…”

Influence of β₃ Integrin Gene Leu³³/Pro³³ Polymorphism on Primary Glomerulonephritis

“…Platelets are sources of a number of mediators (for example platelet-derived growth factor) affecting mesangial function, capillary permeability and glomerular hemodynamics. In situ studies demonstrated an increased amount of platelets and coagulation cascade products in the glomeruli of patients with various forms of glomerulonephritis including IgAN and MGN [12, 13]. Furthermore, there is evidence supporting an involvement of the coagulation system in the pathogenesis of tubulointerstitial damage [14].…”

Relationship of Intraglomerular Coagulation and Platelet Aggregation to Glomerular Sclerosis

“…In the glomeruli of patients with IgA-N, various coagulation-related and platelet membrane anti gens have been observed by immunofluorescent micro scopy [3,[5][6][7][8][9][10], However, only a few studies have at tempted to clarify the role o f intraglomerular coagulation and platelet aggregation in the progression of glomerular injury. The extent of segmental sclerosis is considered to be a prognostic factor in IgA-N [24,25).…”

“…Several investigators have reported on the intraglom erular localization of platelet-related antigens in renal disease [6,[8][9][10]. However, it is difficult to observe the precise status of platelets by immunofluorescence micro scopy or ordinary electron microscopy.…”

“…Intraglomerular coagulation is thought to be involved in the development of glomerular injury [1,2], Several investigators have reported the intraglomerular localiza tion of coagulation-related and platelet membrane anti gens in various glomerular diseases [3][4][5][6][7][8][9][10], The effects of anticoagulants and antiplatelet agents on glomerular dis ease have also been described by some authors [11,12). However, it is still uncertain exactly which glomeruli cause coagulation and platelet aggregation, and how these processes participate in the progression of glomeru lar disease.…”