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Classical ROS-dependent and early/rapid ROS-independent release of Neutrophil Extracellular Traps triggered by Leishmania parasites
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Classical ROS-dependent and early/rapid ROS-independent release of Neutrophil Extracellular Traps triggered by Leishmania parasites
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Journal Article
Classical ROS-dependent and early/rapid ROS-independent release of Neutrophil Extracellular Traps triggered by Leishmania parasites
2015
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Elastase
/ Enzyme Inhibitors - pharmacology
/ Enzymes
/ Extracellular Traps - immunology
/ Extracellular Traps - metabolism
/ Host-Parasite Interactions - immunology
/ Humanities and Social Sciences
/ Humans
/ Hydrolases - antagonists & inhibitors
/ Leukocyte Elastase - antagonists & inhibitors
/ Leukocyte Elastase - immunology
/ Leukocyte Elastase - metabolism
/ NADPH Oxidases - antagonists & inhibitors
/ Oxidation-Reduction - drug effects
/ Peroxidase - antagonists & inhibitors
/ Reactive Oxygen Species - immunology
/ Reactive Oxygen Species - metabolism
/ Science
