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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4615691
- author
- Luo, Lingtao
; Zhang, Su
LU
; Wang, Yongzhi
LU
; Rahman, Milladur
LU
; Syk, Ingvar
LU
; Zhang, Enming
LU
and Thorlacius, Henrik
LU
- organization
- publishing date
- 2014
- 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
- pmid:25085626
- 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
- 2016-04-01 10:06:31
- date last changed
- 2022-04-12 02:00:22
@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}},
doi = {{10.1152/ajplung.00365.2013}},
volume = {{307}},
year = {{2014}},
}