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Antibodies to intercellular adhesion molecule 1/lymphocyte function-associated antigen 1 prevent crescent formation in rat autoimmune glomerulonephritis.
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MedLine Citation:
PMID:  8094735     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In patients with glomerulonephritis widespread crescents are associated with a poor prognosis. Crescent formation appears to depend on the migration of mononuclear cells into Bowman's space, and therefore the interaction between leukocytes and glomerular endothelium may be a critical event in the genesis of crescents. We performed the present study to determine the effects of mouse monoclonal antibodies to the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function-associated antigen 1 (LFA-1) in a model of crescentic glomerulonephritis in Wistar-Kyoto rats, induced by immunization with bovine glomerular basement membrane (GBM). By 10-14 d after immunization, the rats had developed circulating anti-GBM antibodies, reactive with the alpha 3 chain of type IV collagen (the Goodpasture antigen), accompanied by proteinuria, accumulation of rat immunoglobulin (Ig)G in the GBM, increased expression of ICAM-1 by glomerular endothelial cells, infiltration of glomerular tufts with LFA-1+ T cells and monocyte/macrophages, and early crescents. At 5 wk all rats had diffuse fibrocellular crescents, glomerular sclerosis, and tubulointerstitial damage. All rats developed severe renal insufficiency and died by 5 or 6 wk. The administration of monoclonal antibodies to rat ICAM-1 and LFA-1 markedly decreased the severity of the renal disease. In a group of rats injected three times a week with the monoclonal antibodies, from 2 d before immunization with GBM to day 14, glomerular abnormalities and proteinuria were virtually absent at day 14; even at 5 wk glomerular disease was quite mild, with only slight crescent formation and with only a mild decrease in renal function. When treatment was continued until 5 wk, the beneficial effects were even more marked, with virtual absence of crescents and with preservation of normal renal function. In a group of rats in which treatment was initiated on day 14, shortly after the appearance of glomerular abnormalities, progression of the disease was appreciably retarded, and the decrease in renal function was inhibited. The kidneys of rats treated from days -2 to 14 with antibodies to ICAM-1 and LFA-1 showed bright linear staining for rat IgG along the GBM, which did not differ in intensity from that seen in untreated rats. Furthermore, the titers of anti-GBM antibodies at 2 wk in treated rats were not lower than that seen in most of the untreated rats. There was, however, moderate reduction of anti-GBM antibodies at 5 wk in the treated rats.(ABSTRACT TRUNCATED AT 400 WORDS)
Authors:
K Nishikawa; Y J Guo; M Miyasaka; T Tamatani; A B Collins; M S Sy; R T McCluskey; G Andres
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of experimental medicine     Volume:  177     ISSN:  0022-1007     ISO Abbreviation:  J. Exp. Med.     Publication Date:  1993 Mar 
Date Detail:
Created Date:  1993-03-19     Completed Date:  1993-03-19     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2985109R     Medline TA:  J Exp Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  667-77     Citation Subset:  IM    
Affiliation:
Department of Pathology, Massachusetts General Hospital, Boston.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / immunology,  pharmacology*
Autoimmune Diseases / pathology,  physiopathology,  prevention & control*
Basement Membrane / immunology,  pathology
Cell Adhesion Molecules / analysis,  immunology*,  metabolism
Endothelium / chemistry,  immunology,  pathology
Fluorescent Antibody Technique
Glomerulonephritis / pathology,  physiopathology,  prevention & control*
Immunoglobulin G / analysis,  metabolism
Immunohistochemistry
Intercellular Adhesion Molecule-1
Kidney Glomerulus / chemistry,  immunology,  pathology
Leukocytes / chemistry,  immunology,  pathology
Lymphocyte Function-Associated Antigen-1 / analysis,  immunology*,  metabolism
Macrophages / immunology,  pathology
Rats
Rats, Inbred WKY
T-Lymphocytes / immunology,  pathology
Grant Support
ID/Acronym/Agency:
DK-36807/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Cell Adhesion Molecules; 0/Immunoglobulin G; 0/Lymphocyte Function-Associated Antigen-1; 126547-89-5/Intercellular Adhesion Molecule-1
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Full Text
Journal Information
Journal ID (nlm-ta): J Exp Med
ISSN: 0022-1007
ISSN: 1540-9538
Publisher: The Rockefeller University Press
Article Information
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Print publication date: Day: 1 Month: 3 Year: 1993
Volume: 177 Issue: 3
First Page: 667 Last Page: 677
ID: 2190927
Publisher Id: 93171807
PubMed Id: 8094735

Antibodies to intercellular adhesion molecule 1/lymphocyte function- associated antigen 1 prevent crescent formation in rat autoimmune glomerulonephritis


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