Human meconium has high phospholipase A2 activity and induces cellular injury and apoptosis in piglet lungs.
Aspiration of meconium produces an inflammatory reaction resulting in necrotic changes in lung tissue. To further investigate the mechanisms of the meconium-induced early pulmonary injury, twenty 10-12-d-old piglets were studied for lung tissue ultrastructural and apoptotic changes and phospholipase A2 activity. Twelve piglets received an intratracheal bolus (3 mL/kg) of a 20-mg/mL (thin, n = 6) or 65-mg/mL (thick, n = 6) mixture of human meconium, and control piglets (n = 5) received the same amount of intratracheal saline. Three ventilated piglets with no aspiration were also studied. Pulmonary hemodynamics and systemic oxygenation were followed for 6 h after meconium or saline insufflation. In the control groups, the pulmonary tissue showed open alveolar spaces and intact vascular walls, whereas meconium administration resulted in severe pneumonitis, with alveolar spaces filled with inflammatory exudate. Meconium instillation additionally resulted in edematous changes in the vascular walls and alveolar epithelium, whereas type II pneumocytes were intact. The amount of apoptotic cells was increased, especially in the respiratory epithelium, and the catalytic activity of phospholipase A2 in lung tissue samples was significantly elevated after thick meconium instillation. This activity rise proved to be mainly because of human group I phospholipase A2, introduced by meconium. Our data thus show that aspiration of meconium leads to severe lung tissue inflammation with early ultrastructural changes in the pulmonary alveolar walls and is associated with apoptotic cell death in the epithelium, already during the first hours after the insult. These results further suggest that high phospholipase A2 activity, mainly introduced into the lungs within the meconium, may have an important role in the initiation of these alterations in neonatal lungs.
Holopainen
R
R
The Cardiorespiratory Research Unit, University of Turku, Finland.
Aho
H
H
Laine
J
J
Peuravuori
H
H
Soukka
H
H
Kääpä
P
P
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D007322:Instillation, Drug; D007442:Intubation, Intratracheal; D008168:Lung / Q000473:pathology*; D008470:Meconium / Q000201:enzymology / Q000502:physiology*; D008854:Microscopy, Electron; D009195:Peroxidase / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011014:Pneumonia / Q000209:etiology / Q000473:pathology*; D013552:Swine
D009195:Peroxidase; D010741:Phospholipases A; D054467:Phospholipases A2