Wood bark smoke induces lung and pleural plasminogen activator inhibitor 1 and stabilizes its mRNA in porcine lung cells.
Shock
; 36(2): 128-37, 2011 Aug.
Article
en En
| MEDLINE
| ID: mdl-21478814
ABSTRACT
Although aberrant fibrinolysis and plasminogen activator inhibitor 1 (PAI-1) are implicated in acute lung injury, the role of this serpin in the pathogenesis of wood bark smoke (WBS)-induced acute lung injury (SIALI) and its regulation in resident lung cells after exposure to smoke are unclear. A total of 22 mechanically ventilated pigs were included in this study. Immunohistochemical analyses were used to assess fibrin and PAI-1 in the lungs of pigs with SIALI in situ. Plasminogen activator inhibitor 1 was measured in bronchoalveolar lavage fluids by Western blotting. Induction of PAI-1 was determined at the protein and mRNA levels by Western and polymerase chain reaction analyses in primary porcine alveolar type II cells, fibroblasts, and pleural mesothelial cells. Plasminogen activator inhibitor 1 mRNA stability was determined by transcription chase studies. Gel shift analyses were used to characterize the mechanism regulating PAI-1 mRNA stability. Smoke-induced ALI induced PAI-1, with prominent extravascular fibrin deposition in large and small airways as well as alveolar and subpleural compartments. In pleural mesothelial cells, lung fibroblasts, and alveolar type II cells, PAI-1 mRNA was stabilized by WBS extract and contributed to induction of PAI-1. The mechanism involves dissociation of a novel 6-phospho-d-gluconate-NADP oxidoreductase-like PAI-1 mRNA binding protein from PAI-1 mRNA. Exposure to WBS induces prominent airway and mesothelial expression of PAI-1, associated with florid distribution of fibrin in SIALI in vivo Wood bark smoke components induce PAI-1 in vitro in part by stabilization of PAI-1 mRNA, a newly recognized pathway that may promote extravascular fibrin deposition and lung dysfunction in SIALI.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pleura
/
Humo
/
Inhibidor 1 de Activador Plasminogénico
/
Lesión Pulmonar Aguda
/
Pulmón
Límite:
Animals
Idioma:
En
Revista:
Shock
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos