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Apoptotic Cell Clearance in Health and Disease

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Front. Immunol. | doi: 10.3389/fimmu.2018.00288

The neutrophil’s choice: phagocytose vs make NETs

  • 1Immunology, Transplantation & Infectious Diseases, Vita-Salute San Raffaele University, Italy

Neutrophils recognize particulate substrates of microbial or endogenous origin and react by sequestering the cargo via phagocytosis, or by releasing 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, the size of and signals associated to the tethered phagocytic cargo influence the choice of the neutrophil, 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 to diseases characterized by defective phagocytic clearance, such as Systemic Lupus Erythematosus. There is strong potential for novel treatments based on new knowledge of the events determining the inflammatory and pro-thrombotic function of inflammatory leukocytes.

Keywords: Apoptosis, Phagocytosis, platelets, neutrophil extracellular traps (NETs), Clearance

Received: 24 Oct 2017; Accepted: 01 Feb 2018.

Edited by:

Amiram Ariel, University of Haifa, Israel

Reviewed by:

Rostyslav Bilyy, Danylo Halytsky Lviv National Medical University, Ukraine
Moritz Leppkes, Universitätsklinikum Erlangen, Germany  

Copyright: © 2018 Manfredi, Rovere Querini and Maugeri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Angelo A. Manfredi, Vita-Salute San Raffaele University, Immunology, Transplantation & Infectious Diseases, via Olgettina 58, Milan, Italy,