Pulmonary Secretory Phospholipase A2 in Infants with Respiratory Distress Syndrome Stimulates in vitro Neutrophil Migration

Abstract

Background: The massive pulmonary neutrophil influx in respiratory distress syndrome (RDS) in preterm infants has been ascribed to the effect of leukotriene B₄ (LTB₄). Objectives: To investigate whether secretory phospholipase A₂ (sPLA₂), the rate-limiting enzyme in LTB₄ production, is present in lungs of RDS infants and stimulates neutrophil migration. Methods: sPLA₂ 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 sPLA₂ was assessed by addition of its endogenous inhibitor Clara cell protein (CC16) or absorption of sPLA₂ from the aspirates. The role of intracellular signal transduction activation and LTB₄ formation in sPLA₂-induced neutrophil migration was determined using purified sPLA₂, several inhibitors of signal transduction, a LTB₄ synthesis inhibitor and a LTB₄ receptor antagonist. Results: All aspirates contained sPLA₂, which significantly stimulated neutrophil migration. Addition of CC16 or absorption of sPLA₂ abolished the stimulatory effect. All inhibitors significantly reduced sPLA₂-induced neutrophil migration. Conclusions: sPLA₂ is present in tracheal aspirates of preterm infants with RDS. Human recombinant sPLA₂ and pancreatic type sPLA₂ stimulate in vitro cord blood neutrophil migration via activation of intracellular signal transduction pathways, LTB₄ production and receptor binding. We speculate that sPLA₂ contributes to pulmonary neutrophil influx in RDS. Further studies are needed to determine the potential of sPLA₂ inhibition as a treatment for RDS.