Pancreatic phospholipase A2 contributes to lung injury in experimental meconium aspiration.
To investigate the role of pancreatic (group I) secretory PLA2 (sPLA2-I) in the pathogenesis of meconium aspiration syndrome, human particulate meconium or its supernatant either before or after extraction of PLA2-I was insufflated into rat lungs. In addition, the pulmonary effects of intra-tracheal human and bovine PLA2-I were studied. Lungs with saline instillation served as controls. Intrapulmonary particulate meconium (both before and after PLA2-I extraction), unlike meconium supernatant, resulted in markedly elevated lung tissue PLA2 catalytic activity and human PLA2-I concentrations when compared with controls. On the other hand, tissue concentrations of the group II PLA2 remained unchanged in all meconium lungs. Pulmonary PLA2-I concentrations further correlated positively with lung injury scores. Instillation of meconium-derived human PLA2-I, at a concentration of one-third of that in particulate meconium, did not raise PLA2 activity or concentrations of PLA2-I or PLA2-II in the lung tissue from the control level, but still resulted in significantly elevated lung wet/dry ratio and injury score. In contrast, insufflation of bovine pancreatic PLA2 increased the lung tissue enzyme activity and wet/dry ratio from the control level, but had no effect on the type II PLA2 concentration or lung injury score. Our data thus indicate that human pancreatic PLA2, introduced in high amounts within aspirated meconium especially in particulate form, is a potent inducer of lung tissue inflammatory injury.
Sippola
Tomi
T
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Aho
Heikki
H
Peuravuori
Heikki
H
Lukkarinen
Heikki
H
Gunn
Jarmo
J
Kääpä
Pekka
P
D000818:Animals; D002417:Cattle; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000473:pathology; D055370:Lung Injury; D008297:Male; D008471:Meconium Aspiration Syndrome / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D010179:Pancreas / Q000201:enzymology*; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D051381:Rats; D017207:Rats, Sprague-Dawley
D010741:Phospholipases A; D054467:Phospholipases A2