title: Effect of surfactant on pulmonary expression of type IIA PLA(2) in an animal model of acute lung injury.
abstract: We previously showed that the seminatural surfactant Curosurf inhibits the in vitro synthesis of secretory type IIA phospholipase A(2) (sPLA(2)-IIA) in alveolar macrophages (AM). These cells are the main source of sPLA(2)-IIA in a guinea pig model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Here, we investigate the effect of Curosurf on the pulmonary synthesis of sPLA(2)-IIA in this ALI model. Our results showed that intratracheal administration of LPS (330 microg/kg) induced an increase in pulmonary expression of sPLA(2)-IIA, which was inhibited when animals received Curosurf (16 mg/guinea pig) 30 min or 8 h after LPS instillation. When AM were isolated from LPS-treated animals and cultured in conditioned medium, they expressed higher levels of sPLA(2)-IIA than AM from saline-treated animals. This ex vivo sPLA(2)-IIA expression was significantly reduced when guinea pigs received Curosurf 30 min after LPS instillation. Finally, we examined the effect of Curosurf on pulmonary inflammation measured 8 or 24 h after LPS administration. Curosurf instillation 30 min or 8 h after LPS reversed the increase in tumor necrosis factor-alpha expression, polymorphonuclear cell extravasation, and protein concentration in bronchoalveolar lavage fluids. Curosurf also decreased the bronchial reactivity induced by LPS. We conclude that Curosurf inhibits the pulmonary expression of sPLA(2)-IIA and exhibits palliative anti-inflammatory effects in an animal model of ALI.
authors.affiliation: Unité de Défense Innée et Inflammation, Unité Associée Pasteur/Institut National de la Santé et de la Recherche Médicale U485, Institut Pasteur, 25 rue du Dr. Roux, 75015 Paris, France.
authors.forename: Yongzheng
authors.initials: Y
authors.lastname: Wu
authors.forename: Monique
authors.initials: M
authors.lastname: Singer
authors.forename: Françoise
authors.initials: F
authors.lastname: Thouron
authors.forename: Mounia
authors.initials: M
authors.lastname: Alaoui-El-Azher
authors.forename: Lhousseine
authors.initials: L
authors.lastname: Touqui
mesh_terms: D000208:Acute Disease; D000818:Animals; D001688:Biological Products; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D054501:Group II Phospholipases A2; D006168:Guinea Pigs; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D001688:Biological Products; D008070:Lipopolysaccharides; D010743:Phospholipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010741:Phospholipases A; D054501:Group II Phospholipases A2; C068291:poractant alfa