Objectives Secretory phospholipase A2 (sPLA2) is crucial in acute respiratory distress syndrome, causing surfactant degradation. Bile acids are supposed to be toxic for lungs and are implicated in various lung injury forms, such as meconium aspiration, neonatal bile acid pneumonia and reflux aspiration. We sought to study the interaction of sPLA2–bile acids in an extracellular environment.
Methods We collected bronchoalveolar lavage (BAL) fluid from 23 neonates/infants aged less than 6 months with no lung disease, ventilated because of anaesthesia requirement. Used bile acids were in lyophil solution, prepared from human serum matrix. Global enzyme activity in supernatant was measured with an ultrasensitive enzyme immunoassay method in basal conditions. BAL fluid was then randomly assigned to receive bile acids (1 or 5 μmol/litre) or an equivalent volume of saline and sPLA2 was again assessed. Subsequently BAL fluid of neonates was assigned to receive poractant-alfa needed to reach a 6 mg/kg supernatant concentration of phospholipids. This was chosen according to the value found in neonatal BAL fluid after the surfactant therapy for respiratory distress syndrome. sPLA2 was again measured and corrected for dilution factors. Assays were performed after incubation at 37°C for 30 minutes, using continuous photometric reading and serum/supernatant urea ratio was used to normalise sPLA2.
Results Adding highly concentrated bile acids triplicates sPLA2 activity (501.8 (135–1656) IU/ml vs 137.9 (14–399) IU/ml; p = 0.018), whereas insignificant changes were seen with low concentrations/saline. Poractant-alfa reduces sPLA2 activity almost reverting it to the basal activity (118.1 (86.4–131.3) IU/ml; p = 0.01).
Conclusions Bile acids may cause surfactant dysfunction through the enhancement of PLA2 activity, probably acting as a reaction cofactor. Enhancement is reverted by exogenous surfactant. Other mechanisms of bile acid toxicity could exist and deserve to be studied.
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