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

6,9,12,15,18,21-Tetracosahexaenoic acid (24:6n-3) was isolated from a brittle star, Ophiura sarsi Lutken, 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 mu M (27% reduction from the control), and the effect was diminished with increase of the fatty acid concentration (up to 1.00 mu M). These two n-3 PUFA, 20:5n-3 and 22:6n-3, also reduced the histamine content (16 and 20% reduction at 25 mu M, respectively), whereas arachidonic acid (20:4n-6) increased it (18% increase at 25 mu M). Spontaneous- and antigen-induced release of histamine was not influenced with these PUFA (at 25 mu M). 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.