#28 Peroxidation of Phosphatidylcholine: a Signature for Allergen-Induced Airway Responses and Allergen Specificity
The late asthma response (LAR) characterizes the severity of asthma exacerbations, however, mechanisms are elusive. Allergen-challenge induced oxidative stress oxidizes phosphatidylcholine (PC) in the lungs to fragmented (f)/ un-fragmented (un-f) oxidized (Ox) PCs that drive cellular responses important for various disease pathologies. We hypothesize that in asthmatics, allergen induces unique changes in lung OxPCs that are associated to LAR-severity.
Segmental bronchial lavage was collected from 10 adult atopic mild asthmatics, 24 hours post- saline/ allergen challenge on separate days. LAR to saline/ allergen challenge was stratified as mild; moderate; and severe. Lipids were extracted and OxPCs were quantified from the lavage by LC-MS/MS. The correlation of OxPCs with LAR-severity and allergen was deciphered using supervised and unsupervised multivariate models.
13 unique OxPCs in human lung lavage detected had >90% overlap with OxPCs we catalogued in allergen-challenged mice. Total OxPC was similar after saline- (2.7±1.1ng/mL) or allergen-challenge (3.4±1.9 ng/mL). However, multivariate analysis distinguished the association of unique OxPCs with specific allergen and the corresponding LAR- saline triggered mild LAR and had a mixed signature of f- and un-f- OxPCs, while both house dust mite (HDM) and cat allergen induced severe LAR but were associated with different subsets of OxPCs. HDM was strongly associated with the accumulation of fragmented OxPCs while Cat-allergen was associated with un-fragmented OxPCs.
Our unbiased approach has revealed unique relationships between the allergen-induced severity and the abundance of specific bioactive OxPCs, suggesting OxPCs are important in asthma-pathophysiology, and may hold potential to predict disease severity.