Pulmonary Secretory Phospholipase A(2) 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 (LTB4). Objectives: To investigate whether secretory phospholipase A(2) (sPLA(2)), the rate-limiting enzyme in LTB4 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 LTB4 formation in sPLA(2)-induced neutrophil migration was determined using purified sPLA(2), several inhibitors of signal transduction, a LTB4 synthesis inhibitor and a LTB4 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, LTB4 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. Copyright (C) 2009 S. Karger AG, BaselDevelopmen