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Titolo:
EXPRESSION OF INOS, ENOS, AND PEROXYNITRITE-MODIFIED PROTEINS IN EXPERIMENTAL ANTIMYELOPEROXIDASE ASSOCIATED CRESCENTIC GLOMERULONEPHRITIS
Autore:
HEERINGA P; VANGOOR H; MOSHAGE H; KLOK PA; HUITEMA MG; DEJAGER A; SCHEP AJ; 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 GRONINGEN HOSP,DIV GASTROENTEROL & HEPATOL NL-9713 GZ GRONINGEN NETHERLANDS
Titolo Testata:
Kidney international
fascicolo: 2, volume: 53, anno: 1998,
pagine: 382 - 393
SICI:
0085-2538(1998)53:2<382:EOIEAP>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; IMMUNE-COMPLEX GLOMERULONEPHRITIS; GLOMERULI SYNTHESIZE NITRITE; MONOCLONAL-ANTIBODY; CYTOPLASMIC AUTOANTIBODIES; NEPHROTOXIC NEPHRITIS; SYSTEMIC VASCULITIS; ENDOTHELIAL-CELLS; NO SYNTHASE; RAT-KIDNEY;
Keywords:
NITRIC OXIDE RADICALS; ANTIMYELOPEROXIDASE AND CRESCENTIC GN; GLOMERULONEPHRITIS; PEROXYNITRITE-MODIFIED PROTEINS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
52
Recensione:
Indirizzi per estratti:
Citazione:
P. Heeringa et al., "EXPRESSION OF INOS, ENOS, AND PEROXYNITRITE-MODIFIED PROTEINS IN EXPERIMENTAL ANTIMYELOPEROXIDASE ASSOCIATED CRESCENTIC GLOMERULONEPHRITIS", Kidney international, 53(2), 1998, pp. 382-393

Abstract

Nitric oxide radicals are recognized as important mediators in various physiological and pathophysiological processes. During inflammation,increased amounts of nitric oxide (NO) are produced, but it is unclear whether NO radicals are either protective or harmful. To obtain moreinsight into the role of NO in glomerular inflammation, we studied the temporal expression of endothelial NO synthase (eNOS) and inducible NOS (iNOS) in conjunction with platelet aggregation, inflammatory cellinflux, superoxide anion production cells, and nitrotyrosine formation in an experimental model of anti-myeloperoxidase (MPO) associated necrotizing crescentic glomerulonephritis (NCGN). Brown Norway rats wereimmunized with MPO in complete Freund's adjuvant (CFA) or CFA alone. After two weeks, the left kidney was perfused with a neutrophil lysosomal extract and H2O2. Rats were sacrificed at 24 hours, four days, and10 days after perfusion. Kidney sections were stained by immunohistochemistry for eNOS, iNOS, platelets, nitrotyrosines, polymorphonuclear cells (PMN), monocytes, and T-cells. Superoxide anion producing cells were identified by enzyme cytochemistry using diaminobenzidine. Strongstaining for eNOS was found in glomerular capillaries and interstitial tubular capillaries and larger vessels from non-perfused kidneys. At24 hours after perfusion, glomerular and interstitial eNOS staining was greatly reduced, which was associated with massive platelet aggregation. At later time points, eNOS expression was absent in severely damaged glomeruli. Inducible NOS expression was found at all time points in infiltrating inflammatory cells, which by double labeling studies were identified as PMNs and monocytes. The peak in iNOS expression was observed at four days after perfusion but declined thereafter. Superoxide anion and nitrotyrosine generating cells were also found at all time points, bur were most abundantly present at four days after perfusion, coinciding with the peak in iNOS expression. Double labeling experiments revealed that most nitrotyrosine generating cells also producedsuperoxide anions and expressed iNOS. In conclusion, these studies suggest that during the course of anti-MPO associated NCGN, loss of NO production by eNOS in conjunction with NO radical production by iNOS contribute to tissue injury. This is compatible with a protective role for eNOS contrasting with the possibly harmful effects of iNOS in anti-MPO associated NCGN.

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Documento generato il 04/12/20 alle ore 13:17:41