Allergy Asthma Immunol Res.  2014 Jan;6(1):61-65. 10.4168/aair.2014.6.1.61.

Bioactive Lysophosphatidylcholine 16:0 and 18:0 Are Elevated in Lungs of Asthmatic Subjects

• Yoder M
• Zhuge Y
• Yuan Y
• Holian O
• Kuo S
• van Breemen R
• Thomas LL
• Lum H

• KMID: 2166937
• DOI: http://doi.org/10.4168/aair.2014.6.1.61

Abstract

PURPOSE
Asthma is a chronic inflammatory disease of the airways, and is associated with upregulation of phospholipase A2 (PLA2), the enzyme that hydrolyzes phosphatidylcholine, producing lysophosphatidylcholine (LPC) and free fatty acids. LPC is a lipid mediator with known pro-inflammatory and pro-atherogenic properties, and is believed to be a critical factor in cardiovascular diseases. We postulate that asthmatic subjects have an elevated content of LPC in the lung lining fluids.
METHODS
Eight non-asthmatic controls and seven asthmatic subjects were recruited for broncho-alveolar lavage fluids (BALF) collection for analysis of LPC by high performance liquid chromatography-tandem mass spectrometry.
RESULTS
LPC16:0 and LPC18:0 were significantly elevated in the BALF of asthmatics with impaired lung function characteristic of moderate asthma, but not mild asthma. The increased LPC content in BALF was accompanied by increased PLA2 activity. Furthermore, qRT-PCR analysis of the BALF cell fraction indicated increased secretory PLA2-X (sPLA2-X).
CONCLUSIONS
The increased LPC content in the lung lining fluids is a potential critical lipid mediator in the initiation and/or progression of airway epithelial injury in asthma.

Keyword

Lysophosphatidylcholine; asthma; phospholipase A2

MeSH Terms

Asthma
Cardiovascular Diseases
Fatty Acids, Nonesterified
Lung*
Lysophosphatidylcholines*
Mass Spectrometry
Phosphatidylcholines
Phospholipases A2
Therapeutic Irrigation
Up-Regulation
Fatty Acids, Nonesterified
Lysophosphatidylcholines
Phosphatidylcholines
Phospholipases A2

Figure

• 

  Fig. 1 LPC content in BALF. (A) Representative LC-MS-MS chromatograph for LPC16:0, LPC18:0, and LPC18:1 in BALF samples from non-asthmatic and asthmatic subjects; dashed line=non-asthmatic subjects; solid line=moderate-asthmatic subjects; LPC19:0 is internal standard. (B) LPC16:0, LPC18:0, and LPC18:1 reported as average ng/mL+SE; non-asthmatics (n=8), mild-asthmatics (n=3), moderate-asthmatics (n=3). *P<0.05. **P=0.01.

• 

  Fig. 2 PLA2 content in BALF. (A) PLA2 activity of the cell-free fraction of BALF was measured using a fluorescent phosphatidylcholine analog in a microplate assay format. Activity reported as average relative fluorescent units (RFU)+SE. (B) PLA2 mRNA of the cell pellet fraction of BALF was determined by quantitative RT-PCR using primer pairs for human sPLA2-X, sPLA2-XII, cPLA2-IVa, and iPLA2-VI. Results reported in relative copy number normalized to GAPDH as average±SE; non-asthmatics (n=5), moderate-asthmatics (n=4). *P<0.05.

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