fibrin and Serum-Sickness

Glomerular fibrin deposition is important in the pathogenesis of renal failure and crescent formation in glomerulonephritis. The mechanisms of glomerular fibrin deposition are unknown. The current studies explored the role of macrophages in this process. Methods were developed for measuring glomerular fibrin deposition and glomerular procoagulant activity in a passive model of the autologous phase of antiglomerular basement membrane antibody-induced glomerulonephritis in rabbits. Significant fibrin deposition was observed to be associated with glomerular macrophage accumulation. Leukocyte ablation with mustine hydrochloride prevented both glomerular macrophage accumulation and fibrin deposition without affecting the coagulation system or the deposition of disease-inducing antibodies and complement. Repletion with mononuclear inflammatory cells produced significant fibrin deposition. To examine the role of tissue injury per se in glomerular fibrin deposition, a macrophage-independent model of glomerular injury (heterologous phase glomerulonephritis) was also studied. Although a similar degree of glomerular injury occurred, there was no significant fibrin deposition. This suggests that macrophages, rather than injury alone, are responsible for fibrin deposition. Lysates of isolated glomeruli containing macrophages demonstrated greatly enhanced procoagulant activity compared with lysates of glomeruli without macrophages. Thus macrophages appear to be directly responsible for glomerular fibrin deposition in antiglomerular basement membrane antibody-induced glomerulonephritis, and this appears to be due to their ability to express procoagulant activity rather than their propensity to cause glomerular injury.

Topics: Animals; Basement Membrane; Blood Coagulation Tests; Disease Models, Animal; Fibrin; Glomerulonephritis; Immunization, Passive; Inflammation; Kidney Glomerulus; Lymphocyte Depletion; Macrophages; Mechlorethamine; Monocytes; Rabbits; Serum Sickness

Endocardial lesions in acute serum sickness in rabbits were studied with the aid of scanning electron microscopy (SEM). Prominent inflammation developed most often in the ventricular (pocket) side of the mitral valve and was confined to a hollowed area formed between valvular ridges. The early lesion consisted of swelling of endothelial cells with monocytic attachments. Subsequently, frequent endothelial perforations occurred, through which a number of monocytes emigrated into the subendothelial space. Focal or diffuse endothelial desquamation then followed. SEM revealed that the denuded basement membrane also had many perforations enabling monocytic emigration into the deeper valve layer. The accumulated monocytes and proliferating mesenchymal cells produced a granulomatous focus in the valvular tissue in which some monocytes were observed to convert to Anitschkow cells. Infiltration by polymorphs was minimal. Deposition of fibrin occurred in the more severe valvulitic lesions, but no verrucous vegetation formation was observed. The inflammatory process regressed rapidly, leaving focal areas of fibrosis. A possible pathogenesis is discussed in connection with the pathophysiologic conditions of the mitral valve pocket.

Topics: Animals; Basement Membrane; Endocarditis; Endocardium; Endothelium; Fibrin; Microscopy, Electron, Scanning; Mitral Valve; Monocytes; Rabbits; Serum Sickness

Quantitative studies of the effects of defibrination (with ancrod) have been undertaken in two forms of allergic glomerular damage, nephrotoxic serum nephritis and acute serum sickness in rabbits. No differences in intrarenal fixation of nephrotoxic antibody, complement activation or host antibody response were detected between defibrinated and untreated rabbits with nephrotoxic serum nephritis. Defibrination prevented intraglomerular fibrin deposition in this disease; but some glomerular damage as shown by a rise in blood urea and endothelial proliferation still occurred in defibrinated animals. No differences in immune elimination of BSA, circulating immune complex formation or intrarenal localization of immune complexes were noted in defibrinated animals with acute serum sickness. No intraglomerular fibrin deposition was detected in treated or untreated animals in this disease model. It is concluded that the protective effects of ancrod are directly related to defibrination, and not to any other modification of allergic events.

Topics: Ancrod; Animals; Antibodies; Antigen-Antibody Complex; Basement Membrane; Disease Models, Animal; Endopeptidases; Fibrin; Immunoglobulin G; Kidney Glomerulus; Male; Nephritis; Proteinuria; Rabbits; Serum Albumin, Bovine; Serum Sickness; Urea