Identification of compounds that decrease numbers of Mycobacteria in human macrophages in the presence of serum amyloid P.
J Leukoc Biol
; 102(3): 857-869, 2017 09.
Article
em En
| MEDLINE
| ID: mdl-28768708
ABSTRACT
MÏs are a heterogeneous population of cells and include classically activated MÏs (M1) and alternatively activated MÏs (M2). MÏs can change from M1 to M2 and vice versa in response to environmental stimuli. Serum amyloid P (SAP) is a constitutive plasma protein that polarizes MÏs to an M2 phenotype, and part of this effect is mediated through FcγRI receptors. In an effort to find ways to alter MÏs phenotypes, we screened for compounds that can block the SAP-FcγRI interaction. From a screen of 3000 compounds, we found 12 compounds that reduced the ability of fluorescently labeled human SAP to bind cells expressing human FcγRI. Based on cell surface marker expression, 8 of the compounds inhibited the effect of SAP on skewing human MÏs to an M2 phenotype and in the presence of SAP polarized MÏs to an M1 phenotype. In diseases, such as tuberculosis, M1s are more effective at killing bacteria than M2s. SAP potentiated the numbers of the mycobacterial strains Mycobacterium smegmatis and Mycobacterium tuberculosis in MÏs. When added along with SAP, 2 of the compounds reduced intracellular Mycobacterium numbers. Together, these results indicate that the blocking of SAP effects on MÏs can skew these cells toward an M1 phenotype, and this may be useful in treating diseases, such as tuberculosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
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2_ODS3
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3_ND
Base de dados:
MEDLINE
Assunto principal:
Componente Amiloide P Sérico
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Mycobacterium smegmatis
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Macrófagos
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Mycobacterium tuberculosis
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Antituberculosos
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Leukoc Biol
Ano de publicação:
2017
Tipo de documento:
Article