Document Detail


Macrophage-induced glomerular fibrin deposition in experimental glomerulonephritis in the rabbit.
MedLine Citation:
PMID:  4056035     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
S R Holdsworth; P G Tipping
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  76     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1985 Oct 
Date Detail:
Created Date:  1985-11-27     Completed Date:  1985-11-27     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1367-74     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Basement Membrane / immunology
Blood Coagulation Tests
Disease Models, Animal
Fibrin / metabolism*
Glomerulonephritis / etiology,  metabolism*,  pathology
Immunization, Passive
Inflammation
Kidney Glomerulus / immunology,  metabolism*,  pathology
Lymphocyte Depletion
Macrophages / physiology*
Mechlorethamine / pharmacology
Monocytes / physiology
Rabbits
Serum Sickness / complications
Chemical
Reg. No./Substance:
51-75-2/Mechlorethamine; 9001-31-4/Fibrin
Comments/Corrections

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