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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060
EISSN: 1678-8060
Vol. 110, No. 1, 2015, pp. 75-85
Bioline Code: oc15005
Full paper language: English
Document type: Research Article
Document available free of charge

Memórias do Instituto Oswaldo Cruz, Vol. 110, No. 1, 2015, pp. 75-85

 en BAY 41-2272 activates host defence against local and disseminated Candida albicans check for this species in other resources infections
Soeiro-Pereira, Paulo Vítor; Falcai, Angela; Kubo, Christina Arslanian; Antunes, Edson & Condino-Neto, Antonio

Abstract

In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3 -yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans check for this species in other resources and Staphylococcus aureus check for this species in other resources infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41- 2272 might occur primarily by the modulation of the host immune response through macrophage activation.

Keywords
BAY 41-2272; sGC agonist; innate immunity; C. albicans; S. aureus; microbicidal activity

 
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