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1 Unité Institut National de la Santé et de la recherche médicale (INSERM) U.492, Faculté de Médecine de Créteil-Université Paris XII, 2 Unité de Défense Innée et Inflammation, Institut Pasteur, Paris, 3 Laboratoire de Biochimie, Hôpital St Antoine, AP-HP, 4 Service deRéanimation Médicale and 5 Service de Physiologie-Explorations Fonctionnelles, Hôpital Henri Mondor, AP-HP, France
CORRESPONDENCE: C. Delclaux, Unité INSERM U492, Faculté de Médecine de Créteil, 8, ruedu Général Sarrail, 94000 Créteil, France. Fax: 33 148981777. E-mail: delclaux@im3.inserm.fr
Keywords: alpha naphthylthiourea, compliance, endotoxin, Pseudomonas aeruginosa
Received: October 11, 2002
Accepted February 4, 2003
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
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