Pulmonary secretory phospholipase A2 in infants with respiratory distress syndrome stimulates in vitro neutrophil migration.
BACKGROUND
The massive pulmonary neutrophil influx in respiratory distress syndrome (RDS) in preterm infants has been ascribed to the effect of leukotriene B(4) (LTB(4)).


OBJECTIVE
To investigate whether secretory phospholipase A(2) (sPLA(2)), the rate-limiting enzyme in LTB(4) production, is present in lungs of RDS infants and stimulates neutrophil migration.


METHODS
sPLA(2) was measured in tracheal aspirates from 15 preterm infants with RDS. The effect of aspirates on cord blood neutrophil migration was first measured, and the contribution of sPLA(2) was assessed by addition of its endogenous inhibitor Clara cell protein (CC16) or absorption of sPLA(2) from the aspirates. The role of intracellular signal transduction activation and LTB(4) formation in sPLA(2)-induced neutrophil migration was determined using purified sPLA(2), several inhibitors of signal transduction, a LTB(4) synthesis inhibitor and a LTB(4) receptor antagonist.


RESULTS
All aspirates contained sPLA(2), which significantly stimulated neutrophil migration. Addition of CC16 or absorption of sPLA(2) abolished the stimulatory effect. All inhibitors significantly reduced sPLA(2)-induced neutrophil migration.


CONCLUSIONS
sPLA(2) is present in tracheal aspirates of preterm infants with RDS. Human recombinant sPLA(2) and pancreatic type sPLA(2) stimulate in vitro cord blood neutrophil migration via activation of intracellular signal transduction pathways, LTB(4) production and receptor binding. We speculate that sPLA(2) contributes to pulmonary neutrophil influx in RDS. Further studies are needed to determine the potential of sPLA(2) inhibition as a treatment for RDS.
Schrama
Alexandra J J
AJ
Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
Elferink
Jan G R
JG
Hack
C Erik
CE
de Beaufort
Arnout Jan
AJ
Berger
Howard M
HM
Walther
Frans J
FJ
D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054441:Cell Migration Assays, Leukocyte; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D054497:Phospholipases A2, Secretory / Q000378:metabolism* / Q000494:pharmacology*; D012127:Respiratory Distress Syndrome, Newborn / Q000201:enzymology* / Q000473:pathology; D014598:Uteroglobin / Q000494:pharmacology
C556389:SCGB1A1 protein, human; D014598:Uteroglobin; D054497:Phospholipases A2, Secretory