In vivo characterization of neutrophil extracellular traps in various organs of a murine sepsis model

PLoS One. 2014 Nov 5;9(11):e111888. doi: 10.1371/journal.pone.0111888. eCollection 2014.


Neutrophil extracellular traps (NETs) represent extracellular microbial trapping and killing. Recently, it has been implicated in thrombogenesis, autoimmune disease, and cancer progression. The aim of this study was to characterize NETs in various organs of a murine sepsis model in vivo and to investigate their associations with platelets, leukocytes, or vascular endothelium. NETs were classified as two distinct forms; cell-free NETs that were released away from neutrophils and anchored NETs that were anchored to neutrophils. Circulating cell-free NETs were characterized as fragmented or cotton-like structures, while anchored NETs were characterized as linear, reticular, membranous, or spot-like structures. In septic mice, both anchored and cell-free NETs were significantly increased in postcapillary venules of the cecum and hepatic sinusoids with increased leukocyte-endothelial interactions. NETs were also observed in both alveolar space and pulmonary capillaries of the lung. The interactions of NETs with platelet aggregates, leukocyte-platelet aggregates or vascular endothelium of arterioles and venules were observed in the microcirculation of septic mice. Microvessel occlusions which may be caused by platelet aggregates or leukocyte-platelet aggregates and heterogeneously decreased blood flow were also observed in septic mice. NETs appeared to be associated with the formation of platelet aggregates or leukocyte-platelet aggregates. These observational findings may suggest the adverse effect of intravascular NETs on the host during a sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / physiology
  • Cecum / blood supply
  • Cecum / immunology
  • Cecum / metabolism
  • Cecum / pathology
  • Cell Communication
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Extracellular Traps / immunology*
  • Extracellular Traps / metabolism
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Liver / blood supply
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Microcirculation
  • Neutrophil Infiltration / immunology
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Sepsis / immunology*
  • Sepsis / metabolism
  • Sepsis / pathology*
  • Venules / metabolism

Grant support

This work was partly supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (KAKENHI 25462052 to KT and 25462771 to YK). No additional external funding was received for this study. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.