Abstract
Neutrophils recognize particulate substrates of microbial or endogenous origin and react by sequestering the cargo via phagocytosis or by releasing neutrophil extracellular traps (NETs) outside the cell, thus modifying and alerting the environment and bystander leukocytes. The signals that determine the choice between phagocytosis and the generation of NETs are still poorly characterized. Neutrophils that had phagocytosed bulky particulate substrates, such as apoptotic cells and activated platelets, appear to be “poised” in an unresponsive state. Environmental conditions, the metabolic, adhesive and activation state of the phagocyte, and the size of and signals associated with the tethered phagocytic cargo influence the choice of the neutrophils, prompting either phagocytic clearance or the generation of NETs. The choice is dichotomic and apparently irreversible. Defects in phagocytosis may foster the intravascular generation of NETs, thus promoting vascular inflammation and morbidities associated with diseases characterized by defective phagocytic clearance, such as systemic lupus erythematosus. There is a strong potential for novel treatments based on new knowledge of the events determining the inflammatory and pro-thrombotic function of inflammatory leukocytes.
Highlights
Reviewed by: Moritz Leppkes, Universitätsklinikum Erlangen, Germany Rostyslav Bilyy, Danylo Halytsky Lviv National Medical University, Ukraine
Defects in phagocytosis may foster the intravascular generation of neutrophil extracellular traps (NETs), promoting vascular inflammation and morbidities associated with diseases char acterized by defective phagocytic clearance, such as systemic lupus erythematosus
Chromatin decondensation is a prerequisite for NET assembly and depends on the citrullination of histones driven by the PAD4 enzyme [14, 15], by the action of DEK, a nuclear chromatin protein involved in epigenetic and transcriptional regulation [16], and by the concerted action of enzymes, which are partially complexed in the azurophilic primary granules, myeloperoxidase, and elastase
Summary
Received: 24 October 2017 Accepted: 01 February 2018 Published: 20 February 2018. Citation: Manfredi AA, Ramirez GA, Rovere-Querini P and Maugeri N (2018) The Neutrophil’s Choice: Phagocytose vs Make Neutrophil. Neutrophils recognize particulate substrates of microbial or endogenous origin and react by sequestering the cargo via phagocytosis or by releasing neutrophil extracellular traps (NETs) outside the cell, modifying and alerting the environment and bystander leukocytes. The signals that determine the choice between phagocytosis and the gener ation of NETs are still poorly characterized. Neutrophils that had phagocytosed bulky particulate substrates, such as apoptotic cells and activated platelets, appear to be “poised” in an unresponsive state. Environmental conditions, the metabolic, adhesive and activation state of the phagocyte, and the size of and signals associated with the tethered phagocytic cargo influence the choice of the neutrophils, prompting either phagocytic clearance or the generation of NETs. The choice is dichotomic and apparently irreversible. There is a strong potential for novel treatments based on new knowledge of the events determining the inflammatory and pro-thrombotic function of inflammatory leukocytes
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