PMID- 25392950
OWN - NLM
STAT- MEDLINE
DCOM- 20160115
LR  - 20210105
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 11
DP  - 2014
TI  - Presence of neutrophil extracellular traps and citrullinated histone H3 in the 
      bloodstream of critically ill patients.
PG  - e111755
LID - 10.1371/journal.pone.0111755 [doi]
LID - e111755
AB  - Neutrophil extracellular traps (NETs), a newly identified immune mechanism, are 
      induced by inflammatory stimuli. Modification by citrullination of histone H3 is 
      thought to be involved in the in vitro formation of NETs. The purposes of this 
      study were to evaluate whether NETs and citrullinated histone H3 (Cit-H3) are 
      present in the bloodstream of critically ill patients and to identify 
      correlations with clinical and biological parameters. Blood samples were 
      collected from intubated patients at the time of ICU admission from April to June 
      2011. To identify NETs, DNA and histone H3 were visualized simultaneously by 
      immunofluorescence in blood smears. Cit-H3 was detected using a specific 
      antibody. We assessed relationships of the presence of NETs and Cit-H3 with the 
      existence of bacteria in tracheal aspirate, SIRS, diagnosis, WBC count, and 
      concentrations of IL-8, TNF-alpha, cf-DNA, lactate, and HMGB1. Forty-nine patients 
      were included. The median of age was 66.0 (IQR: 52.5-76.0) years. The diagnoses 
      included trauma (7, 14.3%), infection (14, 28.6%), resuscitation from 
      cardiopulmonary arrest (8, 16.3%), acute poisoning (4, 8.1%), heart disease (4, 
      8.1%), brain stroke (8, 16.3%), heat stroke (2, 4.1%), and others (2, 4.1%). We 
      identified NETs in 5 patients and Cit-H3 in 11 patients. NETs and/or Cit-H3 were 
      observed more frequently in "the presence of bacteria in tracheal aspirate" group 
      (11/22, 50.0%) than in "the absence of bacteria in tracheal aspirate" group 
      (4/27, 14.8%) (p<.01). Multiple logistic regression analysis showed that only the 
      presence of bacteria in tracheal aspirate was significantly associated with the 
      presence of NETs and/or Cit-H3. The presence of bacteria in tracheal aspirate may 
      be one important factor associated with NET formation. NETs may play a pivotal 
      role in the biological defense against the dissemination of pathogens from the 
      respiratory tract to the bloodstream in potentially infected patients.
FAU - Hirose, Tomoya
AU  - Hirose T
AD  - Department of Traumatology and Acute Critical Medicine, Osaka University Graduate 
      School of Medicine, Osaka, Japan.
FAU - Hamaguchi, Shigeto
AU  - Hamaguchi S
AD  - Division of Infection Control and Prevention, Osaka University Graduate School of 
      Medicine, Osaka, Japan.
FAU - Matsumoto, Naoya
AU  - Matsumoto N
AD  - Department of Traumatology and Acute Critical Medicine, Osaka University Graduate 
      School of Medicine, Osaka, Japan.
FAU - Irisawa, Taro
AU  - Irisawa T
AD  - Department of Traumatology and Acute Critical Medicine, Osaka University Graduate 
      School of Medicine, Osaka, Japan.
FAU - Seki, Masafumi
AU  - Seki M
AD  - Division of Infection Control and Prevention, Osaka University Graduate School of 
      Medicine, Osaka, Japan.
FAU - Tasaki, Osamu
AU  - Tasaki O
AD  - Department of Emergency Medicine, Unit of Clinical Medicine, Nagasaki University 
      Graduate School of Biomedical Sciences, Nagasaki, Japan.
FAU - Hosotsubo, Hideo
AU  - Hosotsubo H
AD  - Department of Traumatology and Acute Critical Medicine, Osaka University Graduate 
      School of Medicine, Osaka, Japan.
FAU - Yamamoto, Norihisa
AU  - Yamamoto N
AD  - Division of Infection Control and Prevention, Osaka University Graduate School of 
      Medicine, Osaka, Japan.
FAU - Yamamoto, Kouji
AU  - Yamamoto K
AD  - Department of Medical Innovation, Osaka University Hospital, Osaka, Japan.
FAU - Akeda, Yukihiro
AU  - Akeda Y
AD  - International Research Center for Infectious Diseases, Research Institute for 
      Microbial Diseases, Osaka University, Osaka, Japan.
FAU - Oishi, Kazunori
AU  - Oishi K
AD  - International Research Center for Infectious Diseases, Research Institute for 
      Microbial Diseases, Osaka University, Osaka, Japan.
FAU - Tomono, Kazunori
AU  - Tomono K
AD  - Division of Infection Control and Prevention, Osaka University Graduate School of 
      Medicine, Osaka, Japan.
FAU - Shimazu, Takeshi
AU  - Shimazu T
AD  - Department of Traumatology and Acute Critical Medicine, Osaka University Graduate 
      School of Medicine, Osaka, Japan.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20141113
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Histones)
RN  - 29VT07BGDA (Citrulline)
SB  - IM
MH  - Aged
MH  - Bacterial Infections/immunology
MH  - Citrulline/metabolism
MH  - *Critical Illness
MH  - *Extracellular Traps
MH  - Female
MH  - Histones/*blood/metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Neutrophils/*immunology
MH  - Prospective Studies
MH  - Protein Processing, Post-Translational
MH  - Respiratory Tract Infections/immunology
MH  - Trachea/microbiology
PMC - PMC4230949
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/11/14 06:00
MHDA- 2016/01/16 06:00
PMCR- 2014/11/13
CRDT- 2014/11/14 06:00
PHST- 2014/03/09 00:00 [received]
PHST- 2014/09/30 00:00 [accepted]
PHST- 2014/11/14 06:00 [entrez]
PHST- 2014/11/14 06:00 [pubmed]
PHST- 2016/01/16 06:00 [medline]
PHST- 2014/11/13 00:00 [pmc-release]
AID - PONE-D-14-10680 [pii]
AID - 10.1371/journal.pone.0111755 [doi]
PST - epublish
SO  - PLoS One. 2014 Nov 13;9(11):e111755. doi: 10.1371/journal.pone.0111755. 
      eCollection 2014.