Open AccessEicosapentaenoic acid modulates neutrophil leukotriene B 4 receptor expression in cystic fibrosis
Author(s) -
LAWRENCE R. H.,
SORRELL T. C.
Publication year - 1994
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1994.tb06599.x
Subject(s) - leukotriene b4 , receptor , chemotaxis , receptor expression , cell surface receptor , fibrosis , medicine , inflammation , eicosapentaenoic acid , immunology , endocrinology , neutrophile , leukotriene , biology , biochemistry , fatty acid , asthma , polyunsaturated fatty acid
SUMMARY In patients with cystic fibrosis (CF), high intrapulmonary concentrations of the neutrophil chemotaxin leukotriene B 4 (LTB 4 ) are associated with specific reduction of LTB 4 ‐induced chemotaxis of circulating neutrophils. The chemotactic abnormality is partially corrected by dietary supplementation with eicosapentaenoic acid (EPA). LTB 4 ‐induced neutrophil chemotaxis is mediated by specific, high‐affinity, cell surface LTB 4 receptors. The hypotheses that neutrophil LTB 4 receptors are down‐regulated in CF, and that EPA normalizes receptor expression, were tested by measuring the number (R max ) and affinity (K d ) of LTB 4 receptors on neutrophils from eight CF patients before and after EPA (6 weeks of 2–7g/day), and from nine normal individuals. High‐affinity receptor R max was depressed in CF patients (0·6 ± 0·2 × 10 4 /cell (mean ± s.d.) versus 1·8 ± 0·7 × 10 4 /cell in normals), but corrected to normal (2·0 ± 1·9 × 10 4 /cell) after EPA. High‐affinity receptor K d 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 (1·4 ± 1·2 nM). 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 influenced directly by LTB 4 receptor modulation, and that this effect of EPA predominates over alterations in neutrophil signal transduction in situations of chronic exposure to LTB 4 .