Document Detail


Delayed lupus onset in (NZB x NZW)F1 mice expressing a human C-reactive protein transgene.
MedLine Citation:
PMID:  12794828     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Human C-reactive protein (CRP) binds apoptotic cells and alters blood clearance of injected chromatin in mice. To test whether CRP participates in the pathogenesis of systemic lupus erythematosus (SLE), we examined disease development in lupus-prone (NZB x NZW)F(1) (NZB/NZW) mice expressing a human CRP transgene (hCRPtg/BW). METHODS: Mortality was monitored, proteinuria was determined by dipstick, and serum levels of human CRP and anti-double-stranded DNA (anti-dsDNA) were determined by enzyme-linked immunosorbent assay in NZB/NZW and hCRPtg/BW mice. Thin sections of kidneys were analyzed by immunofluorescence microscopy to compare deposition of IgG, IgM, C3, and human CRP, and electron microscopy was used to reveal differences in ultrastructure. In situ hybridization was performed to detect human CRP messenger RNA expression. RESULTS: The hCRPtg/BW mice had less proteinuria and longer survival than NZB/NZW mice. They also had lower IgM and higher IgG anti-dsDNA titers than NZB/NZW mice, although the differences were transient and small. In hCRPtg/BW mice, accumulation of IgM and IgG in the renal glomeruli was delayed, reduced, and more mesangial than in NZB/NZW mice, while end-stage accumulation of IgG, IgM, and C3 in the renal cortex was prevented. There was less glomerular podocyte fusion, basement membrane thickening, mesangial cell proliferation, and occlusion of capillary lumens in hCRPtg/BW mice, but dense deposits in the mesangium were increased. With disease progression in hCRPtg/BW mice, there was little rise in the plasma CRP level, but CRP in the kidneys became increasingly apparent due to local, disease-independent, age-related expression of the transgene. CONCLUSION: In hCRPtg/BW mice, CRP protects against SLE by increasing blood and mesangial clearance of immune complexes and by preventing their accumulation in the renal cortex.
Authors:
Alexander J Szalai; Casey T Weaver; Mark A McCrory; Frederik W van Ginkel; Rachael M Reiman; John F Kearney; Tony N Marion; John E Volanakis
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  48     ISSN:  0004-3591     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-06-09     Completed Date:  2003-07-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1602-11     Citation Subset:  AIM; IM    
Affiliation:
The University of Alabama at Birmingham.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Antinuclear / analysis
C-Reactive Protein / genetics*,  metabolism
Capillaries / ultrastructure
Complement C3 / metabolism
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Genetic Predisposition to Disease
Humans
Immunoglobulin G / metabolism
Immunoglobulin M / metabolism
Kidney Glomerulus / blood supply,  metabolism,  ultrastructure
Longevity
Lupus Erythematosus, Systemic / genetics*,  metabolism,  pathology
Mice
Mice, Inbred C57BL
Mice, Inbred NZB
Mice, Transgenic*
Transgenes
Grant Support
ID/Acronym/Agency:
AI42183/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Antinuclear; 0/Complement C3; 0/Immunoglobulin G; 0/Immunoglobulin M; 9007-41-4/C-Reactive Protein
Comments/Corrections
Comment In:
Arthritis Rheum. 2003 Jun;48(6):1475-7   [PMID:  12794811 ]
Arthritis Rheum. 2004 Feb;50(2):679-80   [PMID:  14872520 ]

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