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Titolo:
Bacille Calmette-Guerin (BCG)-associated inflammation and fibrosis: modulation by recombinant BCG expressing interferon-gamma (IFN-gamma)
Autore:
Wangoo, A; Brown, IN; Marshall, BG; Cook, HT; Young, DB; Shaw, RJ;
Indirizzi:
Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Dept Resp Med, London W2 1PG, England Univ London Imperial Coll Sci Technol & Med London England W2 1PG ngland Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis & Microbiol, London, England Univ London Imperial Coll Sci Technol & Med London England don, England Univ London Imperial Coll Sci Technol & Med, Dept Histopathol, London, England Univ London Imperial Coll Sci Technol & Med London England don, England
Titolo Testata:
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
fascicolo: 1, volume: 119, anno: 2000,
pagine: 92 - 98
SICI:
0009-9104(200001)119:1<92:BC(IAF>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; MYCOBACTERIUM-TUBERCULOSIS INFECTION; ALVEOLAR MACROPHAGES; DEFICIENT MICE; LYMPHOCYTES-T; I PROCOLLAGEN; RESISTANCE; CYTOKINES; MODEL; GENE;
Keywords:
bacille Calmette-Guerin; fibrosis; interferon-gamma;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Wangoo, A Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Dept Resp Med, St Marys Campus,Norfolk Pl, London W2 1PG, England UnivLondon Imperial Coll Sci Technol & Med St Marys Campus,Norfolk Pl London England W2 1PG
Citazione:
A. Wangoo et al., "Bacille Calmette-Guerin (BCG)-associated inflammation and fibrosis: modulation by recombinant BCG expressing interferon-gamma (IFN-gamma)", CLIN EXP IM, 119(1), 2000, pp. 92-98

Abstract

Immunization with existing BCG vaccines has failed to confer consistent protection against tuberculosis. One of the ways to improve the efficacy of BCG is by enhancing its ability to induce a type-1 T cell response. However,this approach carries the risk that enhanced immunoreactivity may exacerbate tissue pathology associated with vaccination. The aim of the present study was to determine whether use of a recombinant BCG expressing IFN-gamma (BCG-IFN) would result in an alteration in the pattern of inflammation and local tissue fibrosis. A murine intravenous BCG infection model was used in which there was a time- and dose-dependent increase in the weight and number of granulomas in the liver. Infection was associated with increased inflammatory activity in the liver, as shown by the increase in expression of inducible nitric oxide synthase (iNOS) assessed by immunochemistry and by measurement of specific mRNA, and in fibrosis measured by hydroxyproline content of the liver and percentage of granuloma cells staining positively for type 1 procollagen. Infection with BCG-IFN resulted in a reduction in organ weight and bacterial load on day 21 compared with infection with control BCG transformed with vector alone (BCG-plasmid). By day 21, there was also a reduction in iNOS mRNA and iNOS(+) cells in granulomas in mice infected with BCG-IFN compared with infection with BCG-plasmid, and a similar reductionin both total number of granulomas and liver hydroxyproline content. Theseresults demonstrate that the granulomas in the areas of mycobacterial infection are active sites of both inflammation and fibrosis, and that the local expression of IFN-gamma by the recombinant BCG results in more efficient bacterial clearance which is accompanied by a reduction in tissue pathology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 16:44:34