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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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Association between in vivo NETs and microcirculation.Approximately 50% of mice were died from a lethal dose of LPS administration. The survived mice were used as LPS treated mice. In the almost dying mice (n = 10) among the LPS treated mice, microvessels were frequently occluded by platelet aggregates or leukocyte-platelet aggregates (A-i, ii; arrows, Movie S9). In some of them, cell-free NETs (red) appeared to be a template for leukocyte-platelet aggregates (A-iii, iv; arrows). Leukocyte-platelet aggregates sometimes included leukocytes with cytoplasmic vacuoles (A-ii; arrowheads). Blood flow speeds of arteriole, venule, and hepatic sinusoid (B) were significantly lower in LPS-treated mice than control, respectively. Data was presented as mean+standard error. *P<0.05, and **P<0.01 versus control, respectively.
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pone-0111888-g006: Association between in vivo NETs and microcirculation.Approximately 50% of mice were died from a lethal dose of LPS administration. The survived mice were used as LPS treated mice. In the almost dying mice (n = 10) among the LPS treated mice, microvessels were frequently occluded by platelet aggregates or leukocyte-platelet aggregates (A-i, ii; arrows, Movie S9). In some of them, cell-free NETs (red) appeared to be a template for leukocyte-platelet aggregates (A-iii, iv; arrows). Leukocyte-platelet aggregates sometimes included leukocytes with cytoplasmic vacuoles (A-ii; arrowheads). Blood flow speeds of arteriole, venule, and hepatic sinusoid (B) were significantly lower in LPS-treated mice than control, respectively. Data was presented as mean+standard error. *P<0.05, and **P<0.01 versus control, respectively.

Mentions: Since the mortality rate at 24 h after the intraperitoneal administration of LPS at a dose of 20 mg/kg was approximately 50%, the survived mice (the other 50% of LPS administered mice) were used as LPS treated mice in this study. We observed that the microvessel appeared to be occluded by platelet aggregates or leukocyte-platelet aggregates in the almost dying mice. (Figure 6-A-i, ii; arrows, Movie S9). In some of them, cell-free NETs appeared to be a template for leukocyte-platelet aggregates (Figure 6-A-iii, iv; arrows). Leukocyte-platelet aggregates sometimes included leukocytes with cytoplasmic vacuoles (Figure 6-A-ii; arrowheads).


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)

Association between in vivo NETs and microcirculation.Approximately 50% of mice were died from a lethal dose of LPS administration. The survived mice were used as LPS treated mice. In the almost dying mice (n = 10) among the LPS treated mice, microvessels were frequently occluded by platelet aggregates or leukocyte-platelet aggregates (A-i, ii; arrows, Movie S9). In some of them, cell-free NETs (red) appeared to be a template for leukocyte-platelet aggregates (A-iii, iv; arrows). Leukocyte-platelet aggregates sometimes included leukocytes with cytoplasmic vacuoles (A-ii; arrowheads). Blood flow speeds of arteriole, venule, and hepatic sinusoid (B) were significantly lower in LPS-treated mice than control, respectively. Data was presented as mean+standard error. *P<0.05, and **P<0.01 versus control, respectively.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0111888-g006: Association between in vivo NETs and microcirculation.Approximately 50% of mice were died from a lethal dose of LPS administration. The survived mice were used as LPS treated mice. In the almost dying mice (n = 10) among the LPS treated mice, microvessels were frequently occluded by platelet aggregates or leukocyte-platelet aggregates (A-i, ii; arrows, Movie S9). In some of them, cell-free NETs (red) appeared to be a template for leukocyte-platelet aggregates (A-iii, iv; arrows). Leukocyte-platelet aggregates sometimes included leukocytes with cytoplasmic vacuoles (A-ii; arrowheads). Blood flow speeds of arteriole, venule, and hepatic sinusoid (B) were significantly lower in LPS-treated mice than control, respectively. Data was presented as mean+standard error. *P<0.05, and **P<0.01 versus control, respectively.
Mentions: Since the mortality rate at 24 h after the intraperitoneal administration of LPS at a dose of 20 mg/kg was approximately 50%, the survived mice (the other 50% of LPS administered mice) were used as LPS treated mice in this study. We observed that the microvessel appeared to be occluded by platelet aggregates or leukocyte-platelet aggregates in the almost dying mice. (Figure 6-A-i, ii; arrows, Movie S9). In some of them, cell-free NETs appeared to be a template for leukocyte-platelet aggregates (Figure 6-A-iii, iv; arrows). Leukocyte-platelet aggregates sometimes included leukocytes with cytoplasmic vacuoles (Figure 6-A-ii; arrowheads).

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