title: Adenovirus-delivered angiopoietin-1 treatment for phosgene-induced acute lung injury.
abstract: BACKGROUND
  Exposure to phosgene can result in an acute lung injury, leading to pulmonary edema and even death. Angiopoietin-1 (Ang1) is a critical factor for vascular stabilization due to its ability to reduce endothelial permeability and inflammation.
  
  
  OBJECTIVE
  In this study, the histopathological changes of the lungs after exposure to phosgene and the effect of Ang1 treatment were examined.
  
  
  METHODS
  Rats were exposed to phosgene gas at 8.33 g/m³ for 5 min. Ang1 overexpressing rats were established by an intravenous injection of adenovirus-Ang1 (Ad/Ang1). The histological changes of the lung were examined by Haematoxylin-Eosin (H&E) staining and fluorescence microscopy. The inferior lobe was used for the determination of the ratio of wet weight to dry weight of the lung. The concentration of cytokines in the serum and bronchoalveolar lavage fluid was determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The pathological analysis showed signs of inflammation and edema, evident from a significant increase in the number of leukocytes in bronchoalveolar lavage fluid and the ratio of wet to dry weight of the lungs. The lung injury induced by phosgene was markedly reduced after the injection of Ad/Ang1. The increase of IL-1β and IL-17 and decrease of vascular endothelial growth factor in the serum and bronchoalveolar lavage fluid of phosgene-exposed animals were abolished by the administration of Ad/Ang1.
  
  
  CONCLUSIONS
  Ang1 has the beneficial effects on phosgene-induced lung injury. The adenovirus-delivered Ang1 may have the potential as a novel approach for the treatment of the acute lung injury caused by phosgene gas inhalation in humans.
authors.affiliation: Center of Emergency & Intensive Care Unit, Jinshan Hospital, Fudan University, 1508 Longhang Road, Shanghai 201508, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yi-Ru
authors.initials: YR
authors.lastname: Shao
authors.forename: Dai-Kun
authors.initials: DK
authors.lastname: He
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Lubna
authors.initials: L
authors.lastname: Nadeem
authors.forename: Guoxiong
authors.initials: G
authors.lastname: Xu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000256:Adenoviridae; D042683:Angiopoietin-1 / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016503:Drug Delivery Systems; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D010705:Phosgene / Q000633:toxicity*; D020011:Protective Agents / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; C467629:Angpt1 protein, rat; D020381:Interleukin-17; D053583:Interleukin-1beta; D020011:Protective Agents; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D010705:Phosgene; D042787:Receptor, TIE-2