RESUMEN
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 and Staphylococcus aureus 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. .
Asunto(s)
Animales , Ratones , Adipocitos Blancos/metabolismo , Ananas/química , Suplementos Dietéticos , Frutas/química , Hipoglucemiantes/aislamiento & purificación , Residuos Industriales/análisis , Extractos Vegetales/aislamiento & purificación , Adipogénesis , Adipocitos Blancos/citología , Antioxidantes/química , Antioxidantes/economía , Antioxidantes/aislamiento & purificación , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/economía , Inhibidores Enzimáticos/aislamiento & purificación , Industria de Procesamiento de Alimentos/economía , Glicosilación , Glicerolfosfato Deshidrogenasa/antagonistas & inhibidores , Glicerolfosfato Deshidrogenasa/metabolismo , Inhibidores de Glicósido Hidrolasas/química , Inhibidores de Glicósido Hidrolasas/economía , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Hipoglucemiantes/química , Hipoglucemiantes/economía , India , Residuos Industriales/economía , Lipotrópicos/química , Lipotrópicos/economía , Lipotrópicos/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/economía , Solventes/química , alfa-Amilasas/antagonistas & inhibidores , alfa-Amilasas/metabolismoRESUMEN
A polysaccharide-rich fraction (ATF) of medicinal mushroom Agaricus brasiliensis was evaluated on the candidacidal activity, H2O2 and nitric oxide (NO) production, and expression of mannose receptors by murine peritoneal macrophages. Mice received three intraperitoneal (i.p.) injections of ATF and after 48 h their peritoneal resident macrophages were assayed against Candida albicans yeast forms. The treatment increased fungicidal activity and it was associated with higher levels of H2O2, whereas NO production was not affected. We also found that the treatment enhances mannose receptor expression by peritoneal macrophages, which are involved in the attachment and phagocytosis of non-opsonized microorganisms. Treatment of animals with ATF was able to enhance the clearance of C. albicans during the first 6 h after the experimental i.p. infection. Our results suggest that this extract can increase host resistance against some infectious agents through the stimulation of microbicidal activity of macrophages.