Nitric oxide-related products and myeloperoxidase in bronchoalveolar lavage fluids from patients with ALI activate NF-kappa B in alveolar cells and monocytes.
[en] An increased production of NO* and peroxynitrite in lungs has been suspected during acute lung injury (ALI) in humans, and recent studies provided evidence for an alveolar production of nitrated compounds. We observed increased concentrations of nitrites/nitrates, nitrated proteins and markers of neutrophil degranulation (myeloperoxidase, elastase and lactoferrine) in the fluids recovered from bronchoalveolar lavage fluids (BALF) of patients with ALI and correlated these changes to the number of neutrophils and the severity of the ALI. We also observed that BALFs stimulated the DNA-binding activity of the nuclear transcription factor kappa B (NF-kappaB) as detected by electrophoretic mobility shift assay in human alveolar cells (A549) and monocytes (THP1). The level of activation of the NF-kappaB-binding activity was correlated to the concentration of nitrated proteins and myeloperoxidase. Furthermore, in vitro studies confirmed that NO*-derived species (peroxynitrite and nitrites) and the neutrophil enzyme myeloperoxidase by themselves increased the activation of NF-kappaB, thereby arguing for an in vivo pathogenetic role of NO*-related products and neutrophil enzymes to human ALI.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Nys, Monique ; Centre Hospitalier Universitaire de Liège - CHU > Soins intensifs - Anesthésie et réanimation
Preiser, Jean-Charles ; Centre Hospitalier Universitaire de Liège - CHU > Soins intensifs
Deby, Ginette ; Centre Hospitalier Universitaire de Liège - CHU > Anesthésie et réanimation
Mathy, Marianne ; Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.)
Damas, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > Soins intensifs
Lamy, Maurice ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
Language :
English
Title :
Nitric oxide-related products and myeloperoxidase in bronchoalveolar lavage fluids from patients with ALI activate NF-kappa B in alveolar cells and monocytes.
Publication date :
2005
Journal title :
Vascular Pharmacology
ISSN :
1537-1891
Publisher :
Elsevier Science, New York, United States - New York
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