Allergen inhalation generates pro-inflammatory oxidised phosphatidylcholine associated with airway dysfunction

Area of Science:

• Biochemistry
• Immunology
• Pulmonology

Background:

• Oxidised phosphatidylcholines (OxPCs) are biomarkers of oxidative stress implicated in various diseases.
• The role of OxPCs in the pathobiology of allergic asthma remains largely uncharacterized.

Purpose of the Study:

• To investigate OxPC profiles in the airways of individuals with airway hyperresponsiveness (AHR) or mild asthma following allergen challenge.
• To determine the contribution of OxPCs to asthma-related pathobiology, including airway narrowing and inflammation.

Main Methods:

• Quantification of OxPC species in bronchoalveolar lavage fluid from human cohorts using ultra-high performance liquid chromatography-tandem mass spectrometry.
• Assessment of OxPC-induced airway narrowing in murine lung slices and evaluation of inflammatory responses in human airway smooth muscle (HASM) cells.
• Analysis of signaling pathways, including protein kinase C, involved in OxPC-mediated effects in HASM cells.

Main Results:

• Distinct OxPC profiles were observed in individuals with and without AHR, correlating with methacholine responsiveness.
• Allergen challenge in mild asthma patients induced unique OxPC signatures associated with late asthma response severity.
• OxPCs induced dose-dependent airway narrowing in murine models and promoted pro-inflammatory responses and oxylipin production in HASM cells via PKC-dependent pathways.

Conclusions:

• OxPCs are present in the airways, increase post-allergen challenge, and correlate with airway dysfunction in asthma.
• OxPCs may contribute to asthma pathogenesis by inducing airway narrowing and promoting airway smooth muscle inflammation and contraction.
• OxPCs represent a potential therapeutic target for managing oxidative stress in asthma.