Phospholipase A₂ is present in meconium and inhibits the activity of pulmonary surfactant: an in vitro study

Abstract

Atelectasis, a major contributor to pulmonary dysfunction in meconium aspiration syndrome (MAS), is produced by bronchiolar obstruction and surfactant inactivation. It has been shown that substances in meconium, e.g. fatty acids, inhibit surfactant activity. However, the role of the enzyme phospholipase A2 (PLA2), which hydrolyses surfactant in adult respiratory distress syndrome (ARDS), has not yet been studied. Our objective was to investigate whether PLA2 is present in meconium and inhibits pulmonary surfactant activity in vitro. Therefore, the presence of PLA2 activity in meconium, collected from 10 newborns, was measured by the formation of lysophosphatidylcholine after incubation of meconium with radioactively labelled dipalmitoylphosphati‐dylcholine. Meconium was fractionated by Sephadex G‐100 column chromatography and the fractions were assayed for PLA2 activity. Also, their effect on the surface tension of surfactant (Curosurf) was measured using a pulsating bubble surfactometer (PBS). PLA2 activity was present in all meconium samples. Addition of meconium to surfactant significantly increased surface tension (mean ± SD: 17 ± 1.6 mN/m to 24.3 ± 6.7 mN/m, p= 0.0001) and only the addition of the PLA2 containing fraction from meconium to surfactant also significantly increased surface tension (mean 1.7 ± 1.6mN/m to 19.0 ± 3.58 mN/m, p < 0.0001). Conclusion: PLA2 is present in meconium and inhibits the activity of pulmonary surfactant in vitro. Therefore, PLA2 in meconium may contribute to surfactant inactivation and alveolar ateectasis in MAS.

Activity and Inhibition Resistance of a Phospholipase-Resistant Synthetic Surfactant in Rat Lungs

“…Phospholipases can be present in the pulmonary interstitium and alveoli during inflammatory lung injury (3-10), and PLA 2 has been proposed as having specific importance in the pathogenesis of ARDS (5,40). PLA 2 is also present in meconium (41), and may contribute to the severe lung injury and respiratory failure found when this substance is aspirated by term infants at birth (42). PLA 2 has also been shown to directly inhibit the surface activity of endogenous lung surfactant (4,41,(43)(44)(45).…”

“…PLA 2 is also present in meconium (41), and may contribute to the severe lung injury and respiratory failure found when this substance is aspirated by term infants at birth (42). PLA 2 has also been shown to directly inhibit the surface activity of endogenous lung surfactant (4,41,(43)(44)(45). As noted earlier, the chemical action of PLA 2 in injured lungs not only can deplete active glycerophospholipids in endogenous and exogenous surfactants, but also produces LPC and fluid-free fatty acids that interact biophysically with intact surfactant to further impair surface activity (11)(12)(13).…”

Secretory phospholipase A2 in newborn infants with sepsis

“…The activity of sPLA 2 was measured by hydrolysis of 2-3 H-linoleylphosphatidyl-ethanolamine 14 and CRP concentration by immunoturbidimetric assay (detection limit 0.3 mg l À1 ). 15 The leukocyte count (corrected for the number of nucleated red cells) was determined in the hematology laboratory and immature/total neutrophil (I/T) ratio calculated.…”

Toxic effects of different meconium fractions on lung function: new therapeutic strategies for meconium aspiration syndrome?

“…Furthermore, the lipid fraction has a stronger inhibitory effect on surfactant function than the water-soluble subfraction. [4][5][6][7] It is well known that bile salts may cause inflammation 8,9 and that FFA, such as oleic acid, induce severe lung failure when administered intravenously. 10 We have tested the effects of different meconium subfractions on pulmonary function in an animal model of newborn piglets.…”