title: Circulating microparticles from septic shock patients exert differential tissue expression of enzymes related to inflammation and oxidative stress.
abstract: 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.
  
  
  METHODS
  Prospective, controlled experiments.
  
  
  METHODS
  Animal basic science laboratory.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: INSERM, U694, Université d'Angers, Angers, France.
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Mastronardi
authors.forename: Hadj Ahmed
authors.initials: HA
authors.lastname: Mostefai
authors.forename: Ferhat
authors.initials: F
authors.lastname: Meziani
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Martínez
authors.forename: Pierre
authors.initials: P
authors.lastname: Asfar
authors.forename: Ramaroson
authors.initials: R
authors.lastname: Andriantsitohaina
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D011446:Prospective Studies; D012772:Shock, Septic / Q000097:blood* / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D051550:I-kappa B Kinase