Contribution to the Study of the Role of Arachidonic Acid Metabolism in Airway Inflammatory Diseases (Nasal polyps, Asthma and Cystic Fibrosis)

Abstract

Eicosanoids are derived from the fatty acids that make up the cell membrane and nuclear membrane. They begin as a single poly unsaturated fatty acid, the arachidonic acid. (AA) is produced from membrane phospholipids and then it can be enzymatically metabolized through the cycloooxygenase pathway into different eicosanoids including prostaglandins. They have various roles in inflammation, and many diseases including asthma, and cystic fibrosis. Fibroblasts from nasal polyps of asthma patients have reduced expression of cyclooxygenase-2 and production of prostaglandin (PG) E2. It is hypothesized that the reported alterations are due to alterations in the availability of AA. So we aimed to determine the fatty acid composition of airway fibroblasts from healthy subjects and from asthma patients with and without aspirin intolerance. In patients with cystic fibrosis there is a relationship between prostanoid production and cystic fibrosis (CF) genotype severity, and also with the severity of the phenotype expression determined by the presence or absence of pancreatic insufficiency. We aimed to assess the relationship in patients with cystic fibrosis between prostanoid production and lung function values, pancreatic function as a measure of CF severity, and genotype severity. And to assess the relationship between PGE-M and PGD-M urinary metabolites of PGE(2) and PGD(2) and CF severity.

Since eicosanoids and their precursor AA have a crucial role in physiology and pathology, it is very important to identify and quantify the amount that is produced by the cells and tissues in order to identify better the targets for pharmaceutical intervention. They need a special method for isolating them and a specific and sensitive instrument for identifying, and quantifying them. Gas chromatography was used for the analysis of fatty acids in human nasal fibroblasts culture, and the high performance liquid chromatography tandem mass spectrometry was used for the identification and quantification of prostaglandins metabolites (Tetranor-PGEM and Tetranor-PGDM) in human urine.