R Ricci-Azevedo1,2, R A Gonçales2, M C Roque-Barreira2, D Girard3. 1. Laboratoire de Recherche en Inflammation et Physiologie des Granulocytes, Université du Québec, INRS-Institut Armand-Frappier, 531 Boul. des Prairies, Laval, QC, H7V 1B7, Canada. 2. Laboratório de Glicobiologia e Imunoquímica, Departamento de Biologia Celular e Molecular da FMRP, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil. 3. Laboratoire de Recherche en Inflammation et Physiologie des Granulocytes, Université du Québec, INRS-Institut Armand-Frappier, 531 Boul. des Prairies, Laval, QC, H7V 1B7, Canada. denis.girard@iaf.inrs.ca.
Abstract
OBJECTIVE AND DESIGN: Paracoccin (PCN), a lectin expressed by Paracoccidioides brasiliensis (Pb), is known to exert activities on the fungal biology, as well as different immune cells of myeloid origin. The aim of this study was to investigate the direct interaction of the recombinant form of the lectin (rPCN) with neutrophils, a neglected area. MATERIALS OR SUBJECTS: Freshly isolated human neutrophils from healthy donors were used. TREATMENT: Neutrophils were incubated with rPCN in vitro. METHODS: After the treatment, the production of reactive oxygen species (ROS), DNA release, IL-8, TNF, IFN-γ, IL-10, IL-12p40, TGF-β and IL-1β production, fungicidal ability, apoptosis and de novo protein synthesis was determined. RESULTS: rPCN was found to induce ROS production as well as DNA release. Using the ROS inhibitor, diphenyleneiodium, both ROS production and DNA release were significantly inhibited. In addition, rPCN was found to induce IL-8 and IL1-β production, inhibit apoptosis and induce de novo protein synthesis. Addition of cycloheximide, a protein synthesis inhibitor, drastically reversed the antiapoptotic effect of rPCN. Finally, the ability to kill Pb yeasts by human neutrophils was significantly increased after rPCN stimulation. CONCLUSIONS: rPCN can alter the biology of human neutrophils increasing their fungicidal ability. Moreover, the ability of rPCN to increase DNA release and to induce suppression of neutrophil apoptosis occurs by a ROS- and de novo protein synthesis-dependent mechanism, respectively.
OBJECTIVE AND DESIGN: Paracoccin (PCN), a lectin expressed by Paracoccidioides brasiliensis (Pb), is known to exert activities on the fungal biology, as well as different immune cells of myeloid origin. The aim of this study was to investigate the direct interaction of the recombinant form of the lectin (rPCN) with neutrophils, a neglected area. MATERIALS OR SUBJECTS: Freshly isolated human neutrophils from healthy donors were used. TREATMENT: Neutrophils were incubated with rPCN in vitro. METHODS: After the treatment, the production of reactive oxygen species (ROS), DNA release, IL-8, TNF, IFN-γ, IL-10, IL-12p40, TGF-β and IL-1β production, fungicidal ability, apoptosis and de novo protein synthesis was determined. RESULTS:rPCN was found to induce ROS production as well as DNA release. Using the ROS inhibitor, diphenyleneiodium, both ROS production and DNA release were significantly inhibited. In addition, rPCN was found to induce IL-8 and IL1-β production, inhibit apoptosis and induce de novo protein synthesis. Addition of cycloheximide, a protein synthesis inhibitor, drastically reversed the antiapoptotic effect of rPCN. Finally, the ability to kill Pbyeasts by human neutrophils was significantly increased after rPCN stimulation. CONCLUSIONS:rPCN can alter the biology of human neutrophils increasing their fungicidal ability. Moreover, the ability of rPCN to increase DNA release and to induce suppression of neutrophil apoptosis occurs by a ROS- and de novo protein synthesis-dependent mechanism, respectively.
Entities:
Keywords:
Apoptosis; Immunomodulation; Neutrophils; Paracoccin; Reactive oxygen species
Authors: Thiago Aparecido da Silva; Maria Aparecida de Souza; Nerry Tatiana Cecílio; Maria Cristina Roque-Barreira Journal: Cell Tissue Res Date: 2014-05-20 Impact factor: 5.249
Authors: Mateus S Freitas; Aline F Oliveira; Thiago A da Silva; Fabrício F Fernandes; Relber A Gonçales; Fausto Almeida; Maria C Roque-Barreira Journal: Front Microbiol Date: 2016-07-05 Impact factor: 5.640