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Published on: May 21, 2018
Circulating microparticles from septic shock patients exert differential tissue expression of enzymes related to
Maria Letizia Mastronardi1, Hadj Ahmed Mostefai, Ferhat Meziani
1INSERM, U694, Université d'Angers, Angers, France.
Objective:
Septic shock is characterized by hypotension and multiple organ failure after infection of microorganisms. Septic shock patients display high levels of circulating microparticles. These are small vesicles released from the plasma membrane of activated or apoptotic cells. Here, we have investigated the effects of in vivo injection of microparticles from nonseptic or septic subjects on protein expression in mouse tissues.
Design:
Prospective, controlled experiments.
Setting:
Animal basic science laboratory.
Subjects:
Male Swiss mice were randomly assigned to one of two groups: 11 animals injected with microparticles isolated from healthy subjects and 15 animals injected with microparticles isolated from septic patients.
Interventions:
Microparticles were extracted from whole blood of septic and nonseptic subjects and were intravenously injected in mice. After 24 hrs, mice were killed and heart, lungs, liver, and kidneys were isolated for Western blot assays. Organs were also used for direct measurements of nitric oxide and superoxide anion production by electron paramagnetic resonance.
Measurements And Main Results:
In heart and lungs, microparticles from septic shock patients increased the expression of endothelial and inducible nitric oxide synthases, cyclooxygenase-2, and nuclear factor-κB. However, extracellular superoxide dismutase was only increased in the heart. These effects were associated either with a greater oxidative or nitrative stress in heart and lungs, without affecting nitric oxide production. The liver exhibited an increase in oxidative stress linked to decreased endothelial nitric oxide synthase and manganese superoxide dismutase expression. However, cyclooxygenase-2 expression and IκBα phosphorylation were decreased. Septic microparticles did not change superoxide anion and nitric oxide productions in kidneys.
Conclusions:
Results suggest that microparticles from septic shock patients exert pleiotropic and differential effects depending on target tissues with regard to the expression of proinflammatory proteins related with nitrative and oxidative stresses. Thus, microparticles might participate in organ dysfunction observed in septic shock patients.
Insights
Microparticles from septic shock patients alter protein expression in mouse organs, suggesting a role in septic shock-induced organ dysfunction. These findings highlight the complex impact of microparticles on oxidative and nitrative stress pathways.
Area of Science:
- Biomedical science
- Pathophysiology
- Molecular biology
Background:
- Septic shock involves hypotension and organ failure, with elevated circulating microparticles in patients.
- Microparticles are vesicles released from cell membranes during activation or apoptosis.
Purpose of the Study:
- To investigate the effects of microparticles from septic and non-septic subjects on protein expression in mouse tissues.
- To determine the impact of microparticles on oxidative and nitrative stress markers in various organs.
Main Methods:
- Prospective, controlled animal experiments were conducted.
- Male Swiss mice received intravenous injections of microparticles from healthy or septic subjects.
- Western blot assays and electron paramagnetic resonance were used to analyze protein expression and stress markers in heart, lungs, liver, and kidneys.
Main Results:
- Septic microparticles increased specific protein expressions (e.g., nitric oxide synthases, cyclooxygenase-2, nuclear factor-κB) in heart and lungs, associated with oxidative/nitrative stress.
- Liver exhibited increased oxidative stress with decreased endothelial nitric oxide synthase and manganese superoxide dismutase, alongside reduced cyclooxygenase-2 and IκBα phosphorylation.
- Kidney function markers (superoxide anion and nitric oxide production) were not altered by septic microparticles.
Conclusions:
- Microparticles from septic shock patients have varied effects on protein expression and stress pathways across different organs.
- These microparticle-induced changes suggest a potential role in the development of organ dysfunction observed in septic shock.
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