Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official VSports app下载. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure V体育官网. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely. .

Review
. 2018 Sep 4:6:109.
doi: 10.3389/fcell.2018.00109. eCollection 2018.

Autophagy in Neutrophils: From Granulopoiesis to Neutrophil Extracellular Traps (V体育2025版)

Panagiotis Skendros  1   2 , Ioannis Mitroulis  1   2   3   4 , Konstantinos Ritis  1   2
Affiliations
Review

"VSports在线直播" Autophagy in Neutrophils: From Granulopoiesis to Neutrophil Extracellular Traps

Panagiotis Skendros et al. Front Cell Dev Biol. .

Abstract

Autophagy is an evolutionarily conserved intracellular degradation system aiming to maintain cell homeostasis in response to cellular stress. At physiological states, basal or constitutive level of autophagy activity is usually low; however, it is markedly up-regulated in response to oxidative stress, nutrient starvation, and various immunological stimuli including pathogens. Many studies over the last years have indicated the implication of autophagy in a plethora of cell populations and functions. In this review, we focus on the role of autophagy in the biology of neutrophils. Early studies provided a link between autophagy and neutrophil cell death, a process essential for resolution of inflammation. Since then, several lines of evidence both in the human system and in murine models propose a critical role for autophagy in neutrophil-driven inflammation and defense against pathogens. Autophagy is essential for major neutrophil functions, including degranulation, reactive oxygen species production, and release of neutrophil extracellular traps VSports手机版. Going back to neutrophil generation in the bone marrow, autophagy plays a critical role in myelopoiesis, driving the differentiation of progenitor cells of the myeloid lineage toward neutrophils. Taken together, in this review we discuss the functional role of autophagy in neutrophils throughout their life, from their production in the bone marrow to inflammatory responses and NETotic cell death. .

Keywords: autophagy; degranulation; granulopoiesis; inflammation; neutrophil; neutrophil extracellular traps; phagocytosis. V体育安卓版.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Autophagy regulates hematopoietic progenitor function. In normal hematopoietic stem cells (HSC), autophagy enables the clearance of damaged mitochondria (mitophagy), promoting the maintenance of HSC function. Dysfunctional autophagy, due to deficiency of autophagy genes Atg7 or Atg12 in mice has been linked to accumulation of mitochondria and metabolic reprogramming toward OXPHOS. This results in functional decline and differentiation toward myeloid lineage.
FIGURE 2
FIGURE 2
The proposed “two-hit” model in autophagy-mediated NETosis. Initially, various stimuli derived from the inflammatory microenvironment stimulate the production of disease-related proteins in naïve neutrophils (first-hit). Subsequently, triggering of autophagy (second-hit) leads to NET formation and the extracellular release of proteins via NET scaffold, contributing to antimicrobial capacity or inflammatory potential of the cell.
FIGURE 3
FIGURE 3
Autophagy in neutrophil biology and disease. Autophagy has a central key role in neutrophil biology by (A) promoting intracellular elimination of pathogens (xenophagy), (B) accelerating phagocytosis (LAP), (C) interplaying with ROS, (D) regulating degranulation, (E) facilitating the resolution of inflammation via NETotic cell death, and (F) leading to externalization of various NET-bound bioactive proteins (depicted as red spherical spots). The enhancement of autophagic machinery (e.g., IVIG, clarithromycin) increases the antimicrobial capacity of neutrophils. On the contrary, blocking autophagy pathway at initial (e.g., IFNλ1, LMWH) or late steps (e.g., HCQ) could be beneficial for neutrophil-driven inflammatory or thrombotic diseases. REDD1/mTOR pathway is a main regulator of autophagy in neutrophils. DAMPS, damage-associated molecular patterns; PAMPS, pathogen-associated molecular patterns; P, phosphorylation; PolyP, inorganic polyphosphate; REDD1, regulated in development and DNA damage responses 1; LAP, LC3-associated phagocytosis; ROS, reactive oxygen species; HCQ, hydroxychloroquine; LMWH, low molecular weight heparin; IVIG, intravenous immunoglobulin; Symbol “?” denotes the possible target of the anti-autophagic action.
See this image and copyright information in PMC

References

    1. Akdis C. A., Ballas Z. K. (2017). The editors’ choice. lessons from familial Mediterranean fever: REDD1 is a novel regulator of stress-induced neutrophilic inflammation. J. Allergy Clin. Immunol. 140 1268–1269. 10.1016/j.jaci.2017.09.007 - DOI
    1. Angelidou I., Chrysanthopoulou A., Mitsios A., Arelaki S., Arampatzioglou A., Kambas K., et al. (2018). REDD1/Autophagy pathway is associated with neutrophil-driven IL-1β inflammatory response in active ulcerative colitis. J. Immunol. 200 3950–3961. 10.4049/jimmunol.1701643 - DOI - PubMed
    1. Apostolidou E., Skendros P., Kambas K., Mitroulis I., Konstantinidis T., Chrysanthopoulou A., et al. (2016). Neutrophil extracellular traps regulate IL-1β-mediated inflammation in familial Mediterranean fever. Ann. Rheum. Dis. 75 269–277. 10.1136/annrheumdis-2014-205958 - V体育官网入口 - DOI - PubMed
    1. Backer J. M. (2016). The intricate regulation and complex functions of the class III phosphoinositide 3-kinase Vps34. Biochem. J. 473 2251–2271. 10.1042/BCJ20160170 - DOI (V体育平台登录) - PubMed
    1. Bhattacharya A., Wei Q., Shin J. N., Abdel Fattah E., Bonilla D. L., Xiang Q., et al. (2015). Autophagy is required for neutrophil-mediated inflammation. Cell Rep. 12 1731–1739. 10.1016/j.celrep.2015.08.019 - DOI - PubMed

LinkOut - more resources