Lipid Mediator Profiling in Pulmonary Disease

Abstract

Oxylipins (e.g. eicosanoids) are endogenous signaling molecules that are formed from fatty acids by mono- or dioxygenase-catalyzed oxygenation and have been shown to play an important role in pathophysiological processes in the lung. These lipid mediators have been extensively studied for their role in inflammation in a broad swathe of respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis and extrinsic allergic alveolitis. Traditional efforts have employed analytical methods (e.g. radio- and enzyme-immunoassay techniques) capable of measuring a limited number of compounds simultaneously. The advent of the omics technologies is changing this approach and methods are being developed for the quantification of small molecules (i.e. metabolomics) as well as lipid-focused efforts (i.e. lipidomics). This review examines in detail the breadth of oxylipins and their biological activity in the respiratory system. In addition, the state-of-the-art methodology in profiling of oxylipins via mass spectrometry is summarized including sample work-up and data processing. These methods will greatly increase our ability to probe oxylipin biology and examine for cross-talk between biological pathways as well as specific compartments in the body. These new data will increase our insight into disease processes and have great potential to identify new biomarkers for disease diagnosis as well as novel therapeutic targets.

Lipid mediator metabolic profiling demonstrates differences in eicosanoid patterns in two phenotypically distinct mast cell populations

“…Oxylipins are signaling lipids formed from fatty acids via mono-or dioxygenase-catalyzed oxygenation that play prominent roles in infl ammatory diseases (6)(7)(8). These compounds include the arachidonic acid (AA)-derived prostaglandins and leukotrienes (LT) as well as analogous compounds produced from an array of polyunsaturated fatty acid substrates [e.g., linoleic acid (LA), ␣ -linolenic acid, docosahexaenoic acid].…”

“…These compounds include the arachidonic acid (AA)-derived prostaglandins and leukotrienes (LT) as well as analogous compounds produced from an array of polyunsaturated fatty acid substrates [e.g., linoleic acid (LA), ␣ -linolenic acid, docosahexaenoic acid]. The biosynthesis of oxylipins is initiated via three major pathways: cyclooxygenase (COX), lipoxygenase (LO), and cytochrome P450 (CYP) (6)(7)(8). The activity of these pathways and the binding of their products to their corresponding receptors are important drug targets for multiple infl ammatory diseases ( 9 ).…”

Application of ’omics technologies to biomarker discovery in inflammatory lung diseases

“…Alternatively, lipid composition may be altered as a result of the disease process and thereby provide biomarkers to stratify the condition, monitor the effect of a drug, or predict the likelihood of exacerbation. Furthermore, the biological importance of lipid metabolic products formed from cell membrane-associated arachidonic acid has been demonstrated in numerous studies [80], although the biological role of structurally analogous compounds remains unclear.…”

“…DHA and EPA), most of which have as of yet undetermined biological roles. The use of LC with low particle size and MRM mass spectrometry has recently made it possible to quantify hundreds of these molecules simultaneously [98,99], providing new insights into their role in respiratory disease [80]. A particular advantage of analysing eicosanoids is that measurement of indicative urinary metabolites is usually a sensitive approach to monitoring pulmonary biosynthesis.…”

“…asthma exacerbations) [100]. There is extensive evidence that monitoring of urinary LTE 4 provides valuable information about mechanisms of inflammation in asthma and other airway diseases [80]. Lipoxins (LX) are short-lived eicosanoids that can support the resolution of inflammation [113].…”