title: Decrease in lung nitric oxide production after peritonitis in mice with sickle cell disease.
abstract: OBJECTIVE
  Nitric oxide bioavailability may limit the occurrence or severity of acute vaso-occlusive episodes in patients with sickle cell disease. Because sepsis is frequently involved in the initiation of vaso-occlusive crisis and acute chest syndrome, we designed the present study in transgenic (SAD) sickle cell mice to investigate whether acute infectious peritonitis affects the enzymatic balance (nitric oxide synthases/arginases) that governs lung nitric oxide production.
  
  
  METHODS
  Controlled animal study.
  
  
  METHODS
  Research laboratory of an academic institution.
  
  
  METHODS
  Transgenic Hbbsingle/single SAD1 (SAD) mice and nontransgenic wild-type littermates (C57/Black mice, control group).
  
  
  METHODS
  Cecal ligation and puncture-induced peritonitis.
  
  
  RESULTS
  We found that 24 hrs after peritonitis, control littermate mice showed an increase in inducible and endothelial nitric oxide synthase messenger RNA and proteins, together with an increase in exhaled nitric oxide (shift of the balance toward nitric oxide synthesis). In contrast, SAD mice, which showed elevated inducible and endothelial nitric oxide synthase protein expression at baseline, showed a marked decrease in nitric oxide synthase proteins, lung nitric oxide end-products, and exhaled nitric oxide after peritonitis, reflecting a shift of the enzymatic balance toward inhibition of nitric oxide synthesis. Peritonitis increased messenger RNA levels of arginase I and arginase II in controls and SAD mice but with a greater increase in arginase I in SAD than in control mice. Peritonitis was associated with a higher mortality rate at 24 hrs in SAD mice. Inhalation of nitric oxide (40 ppm in air) abolished the mortality rate induced by acute peritonitis in SAD mice.
  
  
  CONCLUSIONS
  Acute peritonitis in SAD mice is associated with a defect in lung nitric oxide production and bioavailability that may participate in the acute systemic and lung vaso-occlusive complications of sickle cell disease.
authors.affiliation: Unité INSERM U492-Université Paris XII, Créteil, and Laboratoire de Thérapie Génique Hématopoïétique, Hôpital Saint Louis, Paris, France.
authors.forename: Pablo
authors.initials: P
authors.lastname: Bartolucci
authors.forename: Minh-Triet
authors.initials: MT
authors.lastname: Ngo
authors.forename: Yves
authors.initials: Y
authors.lastname: Beuzard
authors.forename: Frédéric
authors.initials: F
authors.lastname: Galactéros
authors.forename: Guitanouch
authors.initials: G
authors.lastname: Saber
authors.forename: Dominique
authors.initials: D
authors.lastname: Rideau
authors.forename: Saadia
authors.initials: S
authors.lastname: Eddahibi
authors.forename: Bernard
authors.initials: B
authors.lastname: Maitre
authors.forename: Serge
authors.initials: S
authors.lastname: Adnot
authors.forename: Christophe
authors.initials: C
authors.lastname: Delclaux
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications / Q000378:metabolism*; D000818:Animals; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000096:biosynthesis*; D010538:Peritonitis / Q000150:complications / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide