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Titolo:
SYSTEMIC INJECTION OF PRODUCTS OF ACTIVATED NEUTROPHILS AND H2O2 IN MYELOPEROXIDASE-IMMUNIZED RATS LEADS TO NECROTIZING VASCULITIS IN THE LUNGS AND GUT
Autore:
HEERINGA P; FOUCHER P; KLOK PA; HUITEMA MG; TERVAERT JWC; WEENING JJ; KALLENBERG CGM;
Indirizzi:
UNIV GRONINGEN HOSP,DEPT CLIN IMMUNOL,HANZEPLEIN 1 NL-9713 GZ GRONINGEN NETHERLANDS UNIV GRONINGEN HOSP,DEPT PATHOL NL-9713 GZ GRONINGEN NETHERLANDS UNIV AMSTERDAM,ACAD MED CTR,DEPT PATHOL NL-1105 AZ AMSTERDAM NETHERLANDS UNIV DIJON,DEPT PULM F-21004 DIJON FRANCE
Titolo Testata:
The American journal of pathology
fascicolo: 1, volume: 151, anno: 1997,
pagine: 131 - 140
SICI:
0002-9440(1997)151:1<131:SIOPOA>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; WEGENER GRANULOMATOSIS; ENDOTHELIAL-CELLS; ANTIMYELOPEROXIDASE ANTIBODIES; AUTOANTIBODIES; ANTIGEN; MODEL; GLOMERULONEPHRITIS; PROTEINASE-3; BINDING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
P. Heeringa et al., "SYSTEMIC INJECTION OF PRODUCTS OF ACTIVATED NEUTROPHILS AND H2O2 IN MYELOPEROXIDASE-IMMUNIZED RATS LEADS TO NECROTIZING VASCULITIS IN THE LUNGS AND GUT", The American journal of pathology, 151(1), 1997, pp. 131-140

Abstract

The strong association of anti-neutrophil cytoplasmic antibodies withvarious forms of systemic vasculitis suggests a role for these autoantibodies in the pathophysiology of systemic vasculitis. In the presentstudy, we tested the hypothesis that release of neutrophil lysosomal enzymes in the presence of an anti-myeloperoxidase (anti-MPO) immune response may underlie the development of systemic vasculitis. Brown Norway rats were immunized with MPO in complete Freund's adjuvant or complete Freund's adjuvant alone. Two weeks after immunization, rats had developed antibodies to human and rat MPO as measured by enzyme-linked immunosorbent assay. Next, rats were intravenously infused with 400 mug of a human neutrophil lysosomal extract containing 200 mu g of MPO followed by 0.5 ml of a 1 mmol/L solution of H2O2 through a cannula inserted into the right jugular vein. Rats were sacrificed at 4 hours, 24 hours, 7 days, or 14 days, and several organs (lungs, heart, liver, spleen, gut, and kidneys) were examined for vasculitic lesions and inflammatory cell infiltrates. Macroscopically, patchy hemorrhagic spots were observed in the lungs and gut of MPO-immunized rats at days 7 and14 after systemic injection of the neutrophil lysosomal extract and H2O2. Such changes were not observed at earlier time points or in control immunized rats. Histologically, the lungs of MPO-immunized rats sacrificed at days 7 and 14 showed patchy inflammatory cell infiltrates associated with vasculitis, granuloma formation, giant cells, and foci of hemorrhage. At 14 days, early signs of fibrosis were found with deposition of collagen and proliferation of fibroblasts. Furthermore, a prominent leukocytoclastic vasculitis was found in the small intestine of these rats characterized by fibrinoid necrosis and an extensive neutrophilic infiltrate. No inflammatory changes were found in the other organs studied (heart, liver, spleen, and kidneys). Controls immunizedrats, sacrificed at days 7 and 14 showed only some small foci of inflammatory infiltrates in the lungs whereas no inflammatory changes werefound in the gastrointestinal tract. These studies show that release of products from activated neutrophils in the presence of anti-MPO autoantibodies may be relevant to the pathogenesis of anti-MPO-associatedvasculitides.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 22:31:39