Lung surfactant and secretory phospholipase A₂ in inflammatory lung disorders

Surfactant phospholipid composition was studied in the rat, rabbit, and guinea pig. Rabbit surfactant had the most similar composition to human surfactant and the rabbit should be used as an animal model to study diseases where alterations to the surfactant phospholipid composition are deemed to be crucial to the diseases process. The acute asthmatic response was studied by local allergen challenge to mild asthmatics. BALF was obtained from controls and asthmatic subjects before and 24 hours after segmental allergen challenge. There were no differences in the PC or PG compositions between controls and asthmatic subjects before challenge. Allergen challenge in asthmatics but not control volunteers caused a significant increase in the PC to PG ratio because of increased concentrations of PC species containing linoleic acid (16:0/18:2PC, 18:0/18:2PC and 18:1/18:2PC). These molecular species were characteristic of plasma PC analysed from the same subjects, strongly suggesting that altered PC composition in BALF in asthmatic subjects after allergen challenge was due to infiltration of plasma lipoprotein, not to catabolism of surfactant phospholipid. Interactions between surfactant and lipoprotein infiltrate may contribute to surfactant dysfunction and potentiate disease severity in asthma. In vitro studies using ESI-MS demonstrated that purified rabbit surfactant was susceptible to human group IIa sPLA₂ mediated hydrolysis. Preferential hydrolysis of the anionic phospholipid PG as opposed to PC was verified for this enzyme. Further studies of lung surfactant phospholipid compositions in ARDS patients and healthy human control subjects revealed the possible involvement of group IIa sPLA₂ in the pathogenesis of ARDS. However the changes observed during the acute asthmatic response are unlikely to have been caused by the action of sPLA₂.