Induction of type-IIA secretory phospholipase A2 in animal models of acute lung injury.
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| 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.
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| Authors | H L Attalah, Y Wu, M Alaoui-El-Azher, F Thouron, K Koumanov, C Wolf, L Brochard, A Harf, C Delclaux, L Touqui |
| Journal | The European respiratory journal (Eur Respir J) Vol. 21 Issue 6 Pg. 1040-5 (Jun 2003) ISSN: 0903-1936 [Print] England |
| PMID | 12797501 (Publication Type: Journal Article) |
| Chemical References |
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