title: Classical ROS-dependent and early/rapid ROS-independent release of Neutrophil Extracellular Traps triggered by Leishmania parasites.
abstract: Neutrophil extracellular traps (NETs) extruded from neutrophils upon activation are composed of chromatin associated with cytosolic and granular proteins, which ensnare and kill microorganisms. This microbicidal mechanism named classical netosis has been shown to dependent on reactive oxygen species (ROS) generation by NADPH oxidase and also chromatin decondensation dependent upon the enzymes (PAD4), neutrophil elastase (NE) and myeloperoxidase (MPO). NET release also occurs through an early/rapid ROS-independent mechanism, named early/rapid vital netosis. Here we analyze the role of ROS, NE, MPO and PAD4 in the netosis stimulated by Leishmania amazonensis promastigotes in human neutrophils. We demonstrate that promastigotes induce a classical netosis, dependent on the cellular redox imbalance, as well as by a chloroamidine sensitive and elastase activity mechanism. Additionally, Leishmania also induces the early/rapid NET release occurring only 10 minutes after neutrophil-parasite interaction. We demonstrate here, that this early/rapid mechanism is dependent on elastase activity, but independent of ROS generation and chloroamidine. A better understanding of both mechanisms of NET release, and the NETs effects on the host immune system modulation, could support the development of new potential therapeutic strategies for leishmaniasis.
authors.affiliation: Laboratório de Imunobiologia das Leishmanioses, Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, RJ, 21941-902. Brazil.
authors.forename: Natalia C
authors.initials: NC
authors.lastname: Rochael
authors.affiliation: Laboratório de Imunobiologia das Leishmanioses, Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, RJ, 21941-902. Brazil.|Vector Molecular Biology Unit, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, 20852, USA.
authors.forename: Anderson B
authors.initials: AB
authors.lastname: Guimarães-Costa
authors.affiliation: Laboratório de Imunobiologia das Leishmanioses, Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, RJ, 21941-902. Brazil.
authors.forename: Michelle T C
authors.initials: MT
authors.lastname: Nascimento
authors.affiliation: Laboratório de Imunobiologia das Leishmanioses, Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, RJ, 21941-902. Brazil.
authors.forename: Thiago S
authors.initials: TS
authors.lastname: DeSouza-Vieira
authors.affiliation: Laboratório de Bioquímica de Resposta ao Estresse, Instituto de Bioquímica Médica, Programa de Biologia Molecular e Biotecnologia, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-902, Rio de Janeiro, Brazil.|Laboratório de Inflamação e Metabolismo, Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem (INBEB), Universidade Federal do Rio de Janeiro, RJ, 21941-902. Brazil.
authors.forename: Matheus P
authors.initials: MP
authors.lastname: Oliveira
authors.affiliation: Laboratório de Bioquímica de Resposta ao Estresse, Instituto de Bioquímica Médica, Programa de Biologia Molecular e Biotecnologia, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-902, Rio de Janeiro, Brazil.|Laboratório de Inflamação e Metabolismo, Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem (INBEB), Universidade Federal do Rio de Janeiro, RJ, 21941-902. Brazil.
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Garcia e Souza
authors.affiliation: Laboratório de Bioquímica de Resposta ao Estresse, Instituto de Bioquímica Médica, Programa de Biologia Molecular e Biotecnologia, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-902, Rio de Janeiro, Brazil.
authors.forename: Marcus F
authors.initials: MF
authors.lastname: Oliveira
authors.affiliation: Laboratório de Imunobiologia das Leishmanioses, Departamento de Imunologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, RJ, 21941-902. Brazil.
authors.forename: Elvira M
authors.initials: EM
authors.lastname: Saraiva
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D065206:Extracellular Traps / Q000276:immunology* / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D006867:Hydrolases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D007891:Leishmania / Q000276:immunology* / Q000502:physiology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D010084:Oxidation-Reduction / Q000187:drug effects; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D017382:Reactive Oxygen Species / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D009195:Peroxidase; D019255:NADPH Oxidases; D006867:Hydrolases; D019272:Leukocyte Elastase; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases