title: Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis.
abstract: Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined.
  
  
  
  We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia.
  
  
  
  Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis.
  
  
  
  Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism.
  
  
  
  These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.
authors.affiliation: 1 Department of Pulmonary and Critical Care Medicine, KyungHee University Medical Center, Seoul, Republic of Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: 2 Department of Pharmacology and.
authors.forename: Sanjeeb
authors.initials: S
authors.lastname: Shrestha
authors.affiliation: 2 Department of Pharmacology and.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Youn
authors.affiliation: 3 Department of Physiology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Jun-Kyu
authors.initials: JK
authors.lastname: Kim
authors.affiliation: 2 Department of Pharmacology and.
authors.forename: Shin-Yeong
authors.initials: SY
authors.lastname: Kim
authors.affiliation: 4 Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: 5 Department of Pulmonary and Critical Care Medicine, KyungHee University Hospital at Gangdong, Seoul, Republic of Korea.
authors.forename: So-Hee
authors.initials: SH
authors.lastname: Park
authors.affiliation: 2 Department of Pharmacology and.
authors.forename: Won-Gyun
authors.initials: WG
authors.lastname: Ahn
authors.affiliation: 6 Department of Immunology, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Shin
authors.initials: S
authors.lastname: Kim
authors.affiliation: 7 Lung Research Institute of Hallym University, College of Medicine, Hallym University, Chuncheon, Republic of Korea.|8 Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea.
authors.forename: Myung Goo
authors.initials: MG
authors.lastname: Lee
authors.affiliation: 7 Lung Research Institute of Hallym University, College of Medicine, Hallym University, Chuncheon, Republic of Korea.|9 Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea.
authors.forename: Ki-Suck
authors.initials: KS
authors.lastname: Jung
authors.affiliation: 7 Lung Research Institute of Hallym University, College of Medicine, Hallym University, Chuncheon, Republic of Korea.|10 Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Seoul, Republic of Korea; and.
authors.forename: Yong Bum
authors.initials: YB
authors.lastname: Park
authors.affiliation: 7 Lung Research Institute of Hallym University, College of Medicine, Hallym University, Chuncheon, Republic of Korea.|10 Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Seoul, Republic of Korea; and.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Mo
authors.affiliation: 7 Lung Research Institute of Hallym University, College of Medicine, Hallym University, Chuncheon, Republic of Korea.|10 Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Seoul, Republic of Korea; and.
authors.forename: Yousang
authors.initials: Y
authors.lastname: Ko
authors.affiliation: 7 Lung Research Institute of Hallym University, College of Medicine, Hallym University, Chuncheon, Republic of Korea.|8 Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea.
authors.forename: Suh-Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: 11 Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Younsuck
authors.initials: Y
authors.lastname: Koh
authors.affiliation: 1 Department of Pulmonary and Critical Care Medicine, KyungHee University Medical Center, Seoul, Republic of Korea.
authors.forename: Myung Jae
authors.initials: MJ
authors.lastname: Park
authors.affiliation: 2 Department of Pharmacology and.
authors.forename: Dong-Keun
authors.initials: DK
authors.lastname: Song
authors.affiliation: 3 Department of Physiology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Chang-Won
authors.identifier: 0000-0001-7745-9205
authors.initials: CW
authors.lastname: Hong
mesh_terms: D000368:Aged; D000818:Animals; D001343:Autophagy / Q000276:immunology* / Q000502:physiology; D017714:Community-Acquired Infections / Q000276:immunology / Q000503:physiopathology; D004195:Disease Models, Animal; D065206:Extracellular Traps / Q000276:immunology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology; D011014:Pneumonia / Q000276:immunology* / Q000503:physiopathology; D011446:Prospective Studies; D018805:Sepsis / Q000276:immunology* / Q000503:physiopathology*
keywords: autophagy; neutrophil; neutrophil extracellular trap; sepsis