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

Tanaka K, Koike Y, Shimura T, Okigami M, Ide S, Toiyama Y, Okugawa Y, Inoue Y, Araki T, Uchida K, Mohri Y, Mizoguchi A, Kusunoki M - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Departments of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

ABSTRACT
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.

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Related in: MedlinePlus

NETs in pulmonary capillaries of the lung.The excised lungs were investigated immediately after intravital imaging of the cecum and liver to evaluate NETs and endothelial injury. NETs (red) were observed in alveolar space (A-i; arrows) and pulmonary capillaries (A-i; arrowheads) of LPS-treated mice. The number of NETs per FOV and the score of endothelial integrity were determined as described in materials and methods, respectively. The number of NETs per FOV was significantly greater in LPS-treated mice than control mice (B; 6.4±1.1 vs 0.3±0.1). The score of endothelial integrity (C) was lower in LPS treated mice than control mice (2.8±0.2 vs 3.7±0.2). Data was presented as mean+standard error. **P<0.01 versus control.
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pone-0111888-g003: NETs in pulmonary capillaries of the lung.The excised lungs were investigated immediately after intravital imaging of the cecum and liver to evaluate NETs and endothelial injury. NETs (red) were observed in alveolar space (A-i; arrows) and pulmonary capillaries (A-i; arrowheads) of LPS-treated mice. The number of NETs per FOV and the score of endothelial integrity were determined as described in materials and methods, respectively. The number of NETs per FOV was significantly greater in LPS-treated mice than control mice (B; 6.4±1.1 vs 0.3±0.1). The score of endothelial integrity (C) was lower in LPS treated mice than control mice (2.8±0.2 vs 3.7±0.2). Data was presented as mean+standard error. **P<0.01 versus control.

Mentions: NETs were observed in alveolar space (Figure 3-A-i; arrows) and pulmonary capillaries (Figure 3-A-i; arrowheads) of LPS-treated mice. The number of NETs per FOV was significantly greater in LPS-treated mice than control mice (Figure 3-B; 6.4±1.1 vs 0.3±0.1, p<0.01). Circulating cell-free NETs appeared to be entrapped in pulmonary capillaries rather than hepatic sinusoids.


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

Tanaka K, Koike Y, Shimura T, Okigami M, Ide S, Toiyama Y, Okugawa Y, Inoue Y, Araki T, Uchida K, Mohri Y, Mizoguchi A, Kusunoki M - PLoS ONE (2014)

NETs in pulmonary capillaries of the lung.The excised lungs were investigated immediately after intravital imaging of the cecum and liver to evaluate NETs and endothelial injury. NETs (red) were observed in alveolar space (A-i; arrows) and pulmonary capillaries (A-i; arrowheads) of LPS-treated mice. The number of NETs per FOV and the score of endothelial integrity were determined as described in materials and methods, respectively. The number of NETs per FOV was significantly greater in LPS-treated mice than control mice (B; 6.4±1.1 vs 0.3±0.1). The score of endothelial integrity (C) was lower in LPS treated mice than control mice (2.8±0.2 vs 3.7±0.2). Data was presented as mean+standard error. **P<0.01 versus control.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221155&req=5

pone-0111888-g003: NETs in pulmonary capillaries of the lung.The excised lungs were investigated immediately after intravital imaging of the cecum and liver to evaluate NETs and endothelial injury. NETs (red) were observed in alveolar space (A-i; arrows) and pulmonary capillaries (A-i; arrowheads) of LPS-treated mice. The number of NETs per FOV and the score of endothelial integrity were determined as described in materials and methods, respectively. The number of NETs per FOV was significantly greater in LPS-treated mice than control mice (B; 6.4±1.1 vs 0.3±0.1). The score of endothelial integrity (C) was lower in LPS treated mice than control mice (2.8±0.2 vs 3.7±0.2). Data was presented as mean+standard error. **P<0.01 versus control.
Mentions: NETs were observed in alveolar space (Figure 3-A-i; arrows) and pulmonary capillaries (Figure 3-A-i; arrowheads) of LPS-treated mice. The number of NETs per FOV was significantly greater in LPS-treated mice than control mice (Figure 3-B; 6.4±1.1 vs 0.3±0.1, p<0.01). Circulating cell-free NETs appeared to be entrapped in pulmonary capillaries rather than hepatic sinusoids.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Departments of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus