Bile acids cause secretory phospholipase A2 activity enhancement, revertible by exogenous surfactant administration.
OBJECTIVE
Bile acids have been implicated in some forms of acute lung injury, including meconium aspiration and bile acid pneumonia in neonates, or aspiration related ARDS in adults. Secretory phospholipase A2 (sPLA2) is now known as a key enzyme in the lung injury pathways and is supposed to be responsible for surfactant dysfunction. Our aim was to investigate the interaction between bile acids and sPLA2 in an extracellular environment representing an in vitro model of aspiration.


METHODS
In vitro study using broncho-alveolar lavage (BAL) of 23 neonates/infants (<6 m) with healthy lungs. BAL supernatants were assayed for sPLA2 activity in basal condition and after addition of randomly assigned concentrations of bile acids (BA) or normal saline. Samples coming from neonates were then challenged with poractant-alfa up to a phospholipid concentration equal to that found in babies after the surfactant treatment for respiratory distress syndrome. sPLA2 activity was again measured, being corrected for serum/supernatant urea ratio and for confounding factors.


RESULTS
High concentrations of BA (5 micromol/l) significantly increased (P = 0.012) sPLA2 activity, leading to increased surfactant catabolism. This finding was not observed with lower BA concentration and this is consistent with available literature data and may indicate an anionic activation of the enzyme by bile acids. Increased activity was significantly reverted by the addition of exogenous surfactant (P = 0.004) which was able to reduce sPLA2 activity almost to the baseline level.


CONCLUSIONS
BA are likely to contribute to lung injury, causing surfactant inactivation through the increased sPLA2 activity. Other mechanisms cannot be excluded and require further studies to be clarified.
Pediatric Intensive Care Unit, Department of Anaesthesiology and Intensive Care, University Hospital A.Gemelli, Catholic University of the Sacred Heart, L.go A. Gemelli 8, 00168, Rome, Italy. dm.deluca@fastwebnet.it
Daniele
D
De Luca
Angelo
A
Minucci
Enrico
E
Zecca
Marco
M
Piastra
Domenico
D
Pietrini
Virgilio P
VP
Carnielli
Cecilia
C
Zuppi
Ascanio
A
Tridente
Giorgio
G
Conti
Ettore D
ED
Capoluongo
D001647:Bile Acids and Salts / Q000493:pharmacokinetics*; D001688:Biological Products / Q000008:administration & dosage / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid; D005110:Extracellular Space / Q000201:enzymology; D006801:Humans; D007231:Infant, Newborn; D055370:Lung Injury / Q000201:enzymology; D054497:Phospholipases A2, Secretory / Q000187:drug effects* / Q000378:metabolism*; D010743:Phospholipids / Q000008:administration & dosage / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000494:pharmacology*
D001647:Bile Acids and Salts; D001688:Biological Products; D010743:Phospholipids; D011663:Pulmonary Surfactants; D054497:Phospholipases A2, Secretory; C068291:poractant alfa