Presence of neutrophil extracellular traps and citrullinated histone H3 in the bloodstream of critically ill patients.
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-α, 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.
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Tomoya
T
Hirose
Division of Infection Control and Prevention, Osaka University Graduate School of Medicine, Osaka, Japan.
Shigeto
S
Hamaguchi
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Naoya
N
Matsumoto
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Taro
T
Irisawa
Division of Infection Control and Prevention, Osaka University Graduate School of Medicine, Osaka, Japan.
Masafumi
M
Seki
Department of Emergency Medicine, Unit of Clinical Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Osamu
O
Tasaki
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Hideo
H
Hosotsubo
Division of Infection Control and Prevention, Osaka University Graduate School of Medicine, Osaka, Japan.
Norihisa
N
Yamamoto
Department of Medical Innovation, Osaka University Hospital, Osaka, Japan.
Kouji
K
Yamamoto
International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Yukihiro
Y
Akeda
International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Kazunori
K
Oishi
Division of Infection Control and Prevention, Osaka University Graduate School of Medicine, Osaka, Japan.
Kazunori
K
Tomono
Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Takeshi
T
Shimazu
D000368:Aged; D001424:Bacterial Infections / Q000276:immunology; D002956:Citrulline / Q000378:metabolism; D016638:Critical Illness; D065206:Extracellular Traps; D005260:Female; D006657:Histones / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D011446:Prospective Studies; D011499:Protein Processing, Post-Translational; D012141:Respiratory Tract Infections / Q000276:immunology; D014132:Trachea / Q000382:microbiology
D006657:Histones; D002956:Citrulline