Eicosapentaenoic acid modulates neutrophil leukotriene B4 receptor expression in cystic fibrosis

Abstract

SUMMARYIn patients with cystic fibrosis (CF), high intrapulmonary concentrations of the neutrophil chemotaxin leukotriene B4 (LTB4) are associated with specific reduction of LTB4-induced chemotaxis of circulating neutrophils. The chemotactic abnormality is partially corrected by dietary supplementation with eicosapentaenoic acid (EPA). LTB4-induced neutrophil chemotaxis is mediated by specific, high-afiinity, cell surface LTB4 receptors. The hypotheses that neutrophil LTB4 receptors~are down-regulated in CF, and that EPA normalizes receptor expression, were tested by measuring the number (i?n,ax) and affinity {K^) of LTB4 receptors on neutrophils from eight CF patients before and after EPA (6 weeks of 2-7g/day), and from nine normal individuals. High-aifinity receptor R^^,^ was depressed in CF patients (0-6 + 0-2 x 10''/cell (mean + s.d.) versus 1-8 + 0-7 X 10''/cell in normals), but corrected to normal (20 ± 1-9 x lO^/cell) after EPA. Highaffinity receptor K^ was depressed in CF patients (0-4 ± 0-3 nM versus 1 -4 + 0-5 nM in normals), and also corrected to normal with EPA (14 ± 1 2nM). Low-affinity receptors were depressed, but did not change significantly with EPA. These results indicate that neutrophil responses in chronic inflammatory lung disease can be infiuenced directly by LTB4 receptor modulation, and that this effect of EPA predominates over alterations in neutrophil signal transduction in situations of chronic exposure to LTB4.

Candidate Markers Associated with the Probability of Future Pulmonary Exacerbations in Cystic Fibrosis Patients

“…DHA is anti-inflammatory and its metabolites include resolvins and protectins. This imbalance in PUFAs may contribute to the inflammatory status observed in CF [37] , [38] . In fact, our previous studies in a CF mouse model showed improvements in AA and DHA after treatment with fenretinide, a semi-synthetic retinoid, which were concurrent with reductions in inflammatory markers and better clearance of lung infections [25] , [39] .…”

DHA and EPA reverse cystic fibrosis-related FA abnormalities by suppressing FA desaturase expression and activity

“…The fi ndings are representative of at least three independent experiments. by guest, on May 9, 2018 www.jlr.org Downloaded from several of these trials (39)(40)(41). More extensive studies in animal models and CF patients are required to confi rm these early observations.…”

Lipopolysaccharide Induction of Cyclooxygenase-2 in Long-term Nasal Epithelial Cultures in Cystic Fibrosis

“…Chronic neutrophilic airway inflammation is a main characteristic of CF. Previous studies [8][9][10]19,20 on proinflammatory leukotrienes and the COX and 5-lipoxygenase pathways of the respiratory epithelium have shown an impact of the AA cascade on respiratory inflammation in CF. The objective of this study was to investigate whether there is an abnormality in the AA cascade, especially of the COX pathway similar to that in aspirin-intolerant asthma, 14 in the pathogenesis of NPs in CF.…”

“…7 Whereas similar mechanisms in patients with CF and NPs have not yet been investigated, the release of leukotriene B 4 in the bronchopulmonary airways has been examined. [8][9][10] Leukotriene B 4 and other mediators of the 5-lipoxygenase pathway are proinflammatory mediators that are markedly elevated in chronic neutrophilic inflammation. 11 Neutrophilic epithelial invasion is also typically found in CF airway mucosa.…”