R. Holopainen et al., Human meconium has high phospholipase A(2) activity and induces cellular injury and apoptosis in piglet lungs, PEDIAT RES, 46(5), 1999, pp. 626-632
Aspiration of meconium produces an inflammatory reaction resulting in necro
tic changes in lung tissue. To further investigate the mechanisms of the me
conium-induced early pulmonary injury, twenty 10-12-d-old piglets were stud
ied for lung tissue ultrastructural and apoptotic changes and phospholipase
A, 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 meconiu
m, and control piglets (n = 5) received the same amount of intratracheal sa
line. Three ventilated piglets with no aspiration were also studied. Pulmon
ary hemodynamics and systemic oxygenation were followed for 6 h after mecon
ium or saline insulation. In the control groups, the pulmonary tissue showe
d open alveolar spaces and intact vascular walls, whereas meconium administ
ration resulted in severe pneumonitis, with alveolar spaces filled with inf
lammatory exudate. Meconium instillation additionally resulted in edematous
changes in the vascular walls and alveolar epithelium, whereas type II pne
umocytes were intact. The amount of apoptotic cells was increased, especial
ly in the respiratory epithelium, and the catalytic activity of phospholipa
se A, in lung tissue samples was significantly elevated after thick meconiu
m instillation. This activity rise proved to be mainly because of human gro
up I phospholipase A,, introduced by meconium. Our data thus show that aspi
ration of meconium leads to severe lung tissue inflammation with early ultr
astructural changes in the pulmonary alveolar walls and is associated with
apoptotic cell death in the epithelium, already during the first hours afte
r the insult. These results further suggest that high phospholipase A, acti
vity, mainly introduced into the lungs within the meconium, may have an imp
ortant role in the initiation of these alterations in neonatal lungs.