Effect of tetracosahexaenoic acid on the content and release of histamine, and eicosanoid production in MC/9 mouse mast cell

• Published in: Lipids 1998-11, Vol.33 (11), p.1107-1114
• Main Authors: Ishihara, Kenji, Murata, Masakazu, Kaneniwa, Masaki, Saito, Hiroaki, Shinohara, Kazuki, Maeda‐Yamamoto, Mari, Kawasaki, Ken‐ichi, Ooizumi, Tooru
• Format: Article
• Language: English
• Subjects: Animals; Antigens - pharmacology; Cell Line; Diet; Docosahexaenoic Acids - isolation & purification; Docosahexaenoic Acids - pharmacology; Dose-Response Relationship, Drug; Echinodermata - chemistry; Eicosanoids - biosynthesis; Fatty acids; Fatty Acids, Omega-3 - pharmacology; Fish oils; Histamine; Histamine Release - drug effects; Ionophores - pharmacology; Mast Cells - cytology; Mast Cells - drug effects; Mast Cells - metabolism; Mice; Nutrition; Polyunsaturated fatty acids
• ISSN: 0024-4201; 1558-9307
• DOI: 10.1007/s11745-998-0312-9

6,9,12,15,18,21‐Tetracosahexaenoic acid (24∶6n−3) was isolated from a brittle star, Ophiura sarsi Lütken, at>95% purity to evaluate its physiological functions. The effects of 24∶6n−3 on the production of leukotriene (LT)‐related compounds such as LTB4, LTC4 and 5‐hydroxyeicosatetraenoic acid, and the accumulation and release of histamine in an MC/9 mouse mast cell line were studied. We found that 24∶6n−3 could inhibit the antigen‐stimulated production of LT‐related compounds as well as other n−3 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (20∶5n−3) and docosahexaenoic acid (22∶6n−3), which are major n−3 PUFA in fish oils; 24∶6n−3 was also shown to reduce the histamine content in MC/9 cells at 25 μM (27% reduction from the control), and the effect was diminished with increase of the fatty acid concentration (up to 100 μM). These two n−3 PUFA, 20∶5n−3 and 22∶6n−3, also reduced the histamine content (16 and 20% reduction at 25 μM, respectively), whereas arachidonic acid (20∶4n−6) increased it (18% increase at 25 μM). Spontaneous‐ and antigen‐induced release of histamine was not influenced with these PUFA (at 25 μM). Ionophore‐stimulated release of histamine was suppressed by the PUFA (13,9,15, and 11% reduction with 20∶4n−6, 20∶5n−3, 22∶6n−3, and 24∶6n−3, respectively). The patterns of the effects of 24∶6n−3 on the synthesis of eicosanoids and histamine content were more similar to those of 22∶6n−3 than 20∶5n−3. From these results, 24∶6n−3 can be expected to have anti‐inflammatory activity and antiallergic activities similar to those of 22∶6n−3.