Induction of type-IIA secretory phospholipase A2 in animal models of acute lung injury.
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.
Attalah
H L
HL
Unité Institut National de la Santé et de la recherche médicale U.492, Faculté de Médecine de Créteil-Université Paris XII, Créteil, France.
Wu
Y
Y
Alaoui-El-Azher
M
M
Thouron
F
F
Koumanov
K
K
Wolf
C
C
Brochard
L
L
Harf
A
A
Delclaux
C
C
Touqui
L
L
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
D011663:Pulmonary Surfactants; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2