Leukotriene B5 is formed in human neutrophils after dietary supplementation with icosapentaenoic acid.

Abstract

Incorporation and conversion of icosapentaenoic acid (20:5, n - 3) by human polymorphonuclear leukocytes were studied in volunteers (n = 6) ingesting a normal Western diet supplemented with icosapentaenoic acid (approximately equal to 4 g daily). Ingestion of icosapentaenoic acid leads to formation of biologically less active leukotriene B5 (LTB5) from polymorphonuclear leukocytes (PMNL) stimulated with ionophore A23187. LTB5 was identified on HPLC by UV absorption and by GC/MS and showed a behavior identical to that of in vitro synthesized LTB5 produced by incubation of human PMNL with icosapentaenoic acid. The ratio of icosapentaenoic acid/arachidonic acid (20:4, n - 6) in cellular phospholipids increased from 0.045 during control to 0.28 after the supplemented period. LTB5 increased from undetectable values to 70.2 +/- 18.7 pmol of LTB5 per 10(7) PMNL during the experimental period. Synthesis of LTB4 did not change significantly (control, 218.8 +/- 89.1; icosapentaenoic acid-enriched diet, 253.6 +/- 18.7 pmol per 10(7) PMNL). The ratio of LTB4/LTB5 corresponded to the ratio of arachidonic acid/icosapentaenoic acid in PMNL phospholipids. Our findings prove that LTB5, which is 10 to 30 times less potent than LTB4 to cause aggregation, chemotaxis, and degranulation of PMNL, can be formed in vivo in man after dietary icosapentaenoic acid. This may modify the contribution of leukotrienes in processes in which these metabolites are of pathogenetic relevance.