title: Induction of type-IIA secretory phospholipase A2 in animal models of acute lung injury.
abstract: The aim of this study was to evaluate the presence of type-II secretory phospholipase A2 (sPLA2-IIA) in alveolar space and its possible role in the destruction of surfactant in three rat models of acute lung injury. Alveolar instillation of either lipopolysaccaride or live Pseudomonas aeruginosa resulted in a significant increase in lung oedema and in a decrease in static compliance of the respiratory system together with alveolar-neutrophil influx as compared with healthy control rats. The upregulation of messenger ribonucleic acid and sPLA2-IIA by the lung was evident. This was associated with surfactant degradation and a decrease in large:small ratio of surfactant aggregates in bacteria-instilled rats. A negative correlation between compliance and sPLA2-IIA activity in bronchoalveolar lavage fluid was shown. By contrast, during alpha naphthylthiourea-induced injury, neither alveolar-neutrophil influx nor increase in sPLA2-IIA activity was observed. Additional experiments in rats treated with a specific inhibitor of type-II secretory phospholipase A2 activity (3 acetamine-1-benzyl-2 ethylindolyl-5 oxy; propane phosphonic acid (LY311727)) demonstrated no improvement in physiological parameters despite a biochemical effect, suggesting that its activity is only one of the multiple factors involved in the pathophysiology of lung injury.
authors.affiliation: Unité Institut National de la Santé et de la recherche médicale U.492, Faculté de Médecine de Créteil-Université Paris XII, Créteil, France.
authors.forename: H L
authors.initials: HL
authors.lastname: Attalah
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Alaoui-El-Azher
authors.forename: F
authors.initials: F
authors.lastname: Thouron
authors.forename: K
authors.initials: K
authors.lastname: Koumanov
authors.forename: C
authors.initials: C
authors.lastname: Wolf
authors.forename: L
authors.initials: L
authors.lastname: Brochard
authors.forename: A
authors.initials: A
authors.lastname: Harf
authors.forename: C
authors.initials: C
authors.lastname: Delclaux
authors.forename: L
authors.initials: L
authors.lastname: Touqui
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D054501:Group II Phospholipases A2; D008170:Lung Compliance / Q000502:physiology*; D008297:Male; D010741:Phospholipases A / Q000032:analysis* / Q000502:physiology*; D054467:Phospholipases A2; D011014:Pneumonia / Q000150:complications* / Q000503:physiopathology*; D011650:Pulmonary Alveoli / Q000737:chemistry* / Q000503:physiopathology; D011654:Pulmonary Edema / Q000150:complications* / Q000503:physiopathology*; D011663:Pulmonary Surfactants / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000503:physiopathology*; D012720:Severity of Illness Index
chemical_list: D011663:Pulmonary Surfactants; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2