Platelet-activating factor increases reactive oxygen species-mediated microbicidal activity of human macrophages infected with Leishmania (Viannia) braziliensis.

Abstract

Platelet-activating factor (PAF) is produced by macrophages during inflammation and infections. We evaluated whether PAF is able to modulate the infection of human macrophages by Leishmania braziliensis, the main Leishmania sp. in Brazil. Monocyte-derived macrophages were incubated with promastigote forms in absence or presence of exogenous PAF. We observed that the treatment of macrophages with low concentrations of PAF prior to infection increased the phagocytosis of L. braziliensis. More importantly, exogenous PAF reduced the parasitism when it was added before, during or after infection. In addition, treatment with a PAF antagonist (PCA 4248) resulted in a significant increase of macrophage infection in a concentration-dependent manner, suggesting that endogenous PAF is important to control L. braziliensis infection. Mechanistically, while exogenous PAF increased production of reactive oxygen species (ROS) treatment with PCA 4248 reduced oxidative burst during L. braziliensis infection. The microbicidal effects of exogenous PAF were abolished when macrophages were treated with apocynin, an NADPH oxidase inhibitor. The data show that PAF promotes the production of ROS induced by L. braziliensis, suggesting that this lipid mediator may be relevant to control L. braziliensis infection in human macrophages.

• Authors: Arissa Felipe Borges, Camila Imai Morato, Rodrigo Saar Gomes, Miriam Leandro Dorta, Milton Adriano Pelli de Oliveira, Fátima Ribeiro-Dias
• Journal: Pathogens and disease (Pathog Dis) Vol. 75 Issue 7 (09 29 2017) ISSN: 2049-632X [Electronic] United States
• PMID: 28830073 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © FEMS 2017. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Acetophenones
• Dihydropyridines
• Enzyme Inhibitors
• Platelet Activating Factor
• Reactive Oxygen Species
• PCA 4248
• acetovanillone
• NADPH Oxidases

Topics

• Acetophenones (pharmacology)
• Dihydropyridines (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Gene Expression
• Humans
• Leishmania braziliensis (drug effects, growth & development)
• Macrophages (drug effects, immunology, parasitology)
• NADPH Oxidases (antagonists & inhibitors, genetics, metabolism)
• Phagocytosis (drug effects)
• Platelet Activating Factor (antagonists & inhibitors, pharmacology)
• Primary Cell Culture
• Reactive Oxygen Species (agonists, metabolism)
• Respiratory Burst (drug effects)