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Neutrophils express tissue factor in a monkey model of sepsis
H Todoroki1, S Nakamura, A Higure
1Department of Surgery 1, University of Occupational and Environmental Health, Kitakyushu, Japan.
Background:
Although tissue factor (TF) is involved in hemostasis, thrombogenesis, inflammation, and cellular immune response, its source in sepsis remains controversial. Recently, we found that, in addition to monocytes and endothelial cells, neutrophils may express TF in a rabbit model. The purpose of this study was to determine whether neutrophils could be a source of TF in a monkey model of sepsis.
Methods:
TF messenger RNA (mRNA) and protein in neutrophils were assayed by in situ hybridization and immunohistochemistry in tissues obtained from monkeys after injection of lipopolysaccharide (LPS) (n = 3) and after injection of saline as a control (n = 2). Coagulation parameters were measured before and at 1.5 and 3 hours after injections.
Results:
In LPS-treated monkeys, TF mRNA and protein were induced not only in monocytes and endothelial cells, but also in neutrophils accumulating in the liver 3 hours after LPS injection. Thrombin-antithrombin III complex and fibrin degradation products D-dimer levels were significantly increased at 3 and 1.5 hours after LPS injection compared with controls.
Conclusions:
Neutrophils are a source of TF and are implicated in direct activation of the coagulation cascade in the early phases of sepsis in the monkey. These results give important information for the treatment of sepsis.
Insights
Neutrophils express tissue factor (TF) in sepsis, contributing to coagulation activation. This finding in a monkey model offers insights into sepsis treatment strategies.
Area of Science:
- Immunology
- Hematology
- Pathophysiology
Background:
- Tissue factor (TF) plays a role in hemostasis, thrombogenesis, inflammation, and immune responses.
- The precise source of TF during sepsis has been a subject of ongoing research and debate.
- Previous studies suggested neutrophils might express TF, but further investigation was needed.
Purpose of the Study:
- To investigate whether neutrophils serve as a source of TF in a primate model of sepsis.
- To elucidate the role of neutrophils in TF expression during the early stages of sepsis.
Main Methods:
- Assessed TF messenger RNA (mRNA) and protein in neutrophils using in situ hybridization and immunohistochemistry.
- Utilized a lipopolysaccharide (LPS)-induced sepsis model in monkeys, with saline-injected controls.
- Monitored coagulation parameters at various time points post-injection.
Main Results:
- TF mRNA and protein were detected in neutrophils, monocytes, and endothelial cells in LPS-treated monkeys.
- Neutrophils expressing TF were observed accumulating in the liver three hours after LPS administration.
- Significant increases in thrombin-antithrombin III complex and D-dimer levels indicated coagulation activation.
Conclusions:
- Neutrophils are confirmed as a source of TF during sepsis in the monkey model.
- Neutrophil-derived TF is implicated in the direct activation of the coagulation cascade in early sepsis.
- These findings provide crucial information for developing therapeutic interventions for sepsis.