Microparticles induce variable levels of activation in macrophages infected with Mycobacterium tuberculosis.
Tuberculosis (Edinb)
; 90(3): 188-96, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-20382085
ABSTRACT
Activation of human macrophages infected with Mycobacterium tuberculosis was investigated following exposure to microparticles (MP) possessing high anti-tubercular efficacy in mice. A small set of innate responses (cytokine profiles, NO production, Annexin-V staining and caspase-8, caspase-9 and caspase-3 activities) of differentiated THP-1 cells or human monocyte-derived macrophages infected 110 in vitro were compared. Cytokines of THP-1 macrophages were comparable in trends, but not in magnitude, with five human genotypes studied. MP reversed suppression of tumor necrosis factor induced by infection, and transiently upregulated gamma-interferon. Drug-free MP surprisingly induced gamma-interferon, but not tumor necrosis factor. Primary cells responded to MP, regardless of drug content, by upregulation of NO; but THP-1 cells did not respond to drug-free MP. About 19% of infected cells exposed to MP underwent apoptosis compared to approximately 11% cells treated otherwise. Cell death induced by drug-free MP was caspase independent. Intracellular bacterial survival varied between individuals. Untreated infection resulted in survival of 900+/-141 cfu; exposure to soluble drugs, drug-containing and blank microparticles respectively, reduced CFU counts to <10, <10 and 102+/-139. These observations indicate that despite variations in magnitude between cells from different sources, innate responses conducive to killing intracellular bacteria were evoked by inhalable MP.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Citocinas
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Micropartículas Derivadas de Células
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Ativação de Macrófagos
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Macrófagos
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Mycobacterium tuberculosis
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article