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Pro-inflammatory role of neutrophil extracellular traps in abdominal sepsis.

Luo, Lingtao; Zhang, Su LU ; Wang, Yongzhi LU ; Rahman, Milladur LU ; Syk, Ingvar LU ; Zhang, Enming LU and Thorlacius, Henrik LU (2014) In American Journal of Physiology: Lung Cellular and Molecular Physiology 307(7). p.586-596
Abstract
Excessive neutrophil activation is a major component in septic lung injury. Neutrophil-derived DNA may form extracellular traps in response to bacterial invasions. The aim of the present study was to investigate the potential role of neutrophil extracellular traps (NETs) in septic lung injury. Male C57BL/6 mice were treated with rhDNAse (5 mg/kg) after cecal ligation and puncture (CLP). Extracellular DNA was stained by Sytox green and NET formation was quantified by confocal microscopy and cell-free DNA in plasma, peritoneal cavity and lung. Blood, peritoneal fluid and lung tissue were harvested for analysis of neutrophil infiltration, NET levels, tissue injury as well as CXC chemokine and cytokine formation. We observed that CLP caused... (More)
Excessive neutrophil activation is a major component in septic lung injury. Neutrophil-derived DNA may form extracellular traps in response to bacterial invasions. The aim of the present study was to investigate the potential role of neutrophil extracellular traps (NETs) in septic lung injury. Male C57BL/6 mice were treated with rhDNAse (5 mg/kg) after cecal ligation and puncture (CLP). Extracellular DNA was stained by Sytox green and NET formation was quantified by confocal microscopy and cell-free DNA in plasma, peritoneal cavity and lung. Blood, peritoneal fluid and lung tissue were harvested for analysis of neutrophil infiltration, NET levels, tissue injury as well as CXC chemokine and cytokine formation. We observed that CLP caused increased formation of NETs in the plasma, peritoneal cavity and lung. Administration of rhDNAse not only eliminated NET formation in the plasma, peritoneal cavity and bronchoalveolar space but also reduced lung edema and tissue damage 24 h after CLP induction. Moreover, treatment with rhDNAse decreased CLP-induced formation of CXC chemokines, IL-6 and HMGB1 in the plasma as well as CXC chemokines and IL-6 in the lung. In vitro, we found that neutrophil-derived NETs had the capacity to stimulate secretion of CXCL2, TNF-α and HMGB1 from alveolar macrophages. Taken together, our findings show that NETs regulate pulmonary infiltration of neutrophils and tissue injury via formation of pro-inflammatory compounds in abdominal sepsis. Thus, we conclude that NETs exert a pro-inflammatory role in septic lung injury. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
American Journal of Physiology: Lung Cellular and Molecular Physiology
volume
307
issue
7
pages
586 - 596
publisher
American Physiological Society
external identifiers
  • pmid:25085626
  • wos:000343245600009
  • scopus:84907539525
ISSN
1522-1504
DOI
10.1152/ajplung.00365.2013
language
English
LU publication?
yes
id
28217a15-f9fe-41b8-b85e-56bcb2321bf4 (old id 4615691)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25085626?dopt=Abstract
date added to LUP
2014-09-03 20:31:33
date last changed
2017-11-05 03:06:05
@article{28217a15-f9fe-41b8-b85e-56bcb2321bf4,
  abstract     = {Excessive neutrophil activation is a major component in septic lung injury. Neutrophil-derived DNA may form extracellular traps in response to bacterial invasions. The aim of the present study was to investigate the potential role of neutrophil extracellular traps (NETs) in septic lung injury. Male C57BL/6 mice were treated with rhDNAse (5 mg/kg) after cecal ligation and puncture (CLP). Extracellular DNA was stained by Sytox green and NET formation was quantified by confocal microscopy and cell-free DNA in plasma, peritoneal cavity and lung. Blood, peritoneal fluid and lung tissue were harvested for analysis of neutrophil infiltration, NET levels, tissue injury as well as CXC chemokine and cytokine formation. We observed that CLP caused increased formation of NETs in the plasma, peritoneal cavity and lung. Administration of rhDNAse not only eliminated NET formation in the plasma, peritoneal cavity and bronchoalveolar space but also reduced lung edema and tissue damage 24 h after CLP induction. Moreover, treatment with rhDNAse decreased CLP-induced formation of CXC chemokines, IL-6 and HMGB1 in the plasma as well as CXC chemokines and IL-6 in the lung. In vitro, we found that neutrophil-derived NETs had the capacity to stimulate secretion of CXCL2, TNF-α and HMGB1 from alveolar macrophages. Taken together, our findings show that NETs regulate pulmonary infiltration of neutrophils and tissue injury via formation of pro-inflammatory compounds in abdominal sepsis. Thus, we conclude that NETs exert a pro-inflammatory role in septic lung injury.},
  author       = {Luo, Lingtao and Zhang, Su and Wang, Yongzhi and Rahman, Milladur and Syk, Ingvar and Zhang, Enming and Thorlacius, Henrik},
  issn         = {1522-1504},
  language     = {eng},
  number       = {7},
  pages        = {586--596},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Lung Cellular and Molecular Physiology},
  title        = {Pro-inflammatory role of neutrophil extracellular traps in abdominal sepsis.},
  url          = {http://dx.doi.org/10.1152/ajplung.00365.2013},
  volume       = {307},
  year         = {2014},
}