Consequences of eicosapentaenoic acid (n-3) and arachidonic acid (n-6) supplementation on mast cell mediators

Mast cells are important players in the pathogenesis of atopic diseases. These cells release immediate-phase and late-phase mediators of inflammation. Fatty acids are incorporated in cellular membranes and therefore seem to influence mediator production and release. A study was conducted to assess the effects of eicosapentaenoic acid (EPA, 20:5n-3) and arachidonic acid (AA, 20:4n-6) on mast cell mediators in a canine mastocytoma cell line (C2). Cells were cultured in a basic medium (Dulbecco's modified Eagle's medium/HAM's F12 1:1, DEH), DEH supplemented with 14.0 muM EPA (DEH-EPA) or 14 muM AA (DEH-AA). The DEH-AA cultured cells had increased spontaneous and mastoparan-stimulated PGE(2) production and histamine release. Furthermore, the tryptase activity was increased. The DEH-EPA cultured cells rendered elevated levels of PGE(2) and histamine release compared with DEH only after stimulation. These levels were significantly lower in comparison to DEH-AA. The increased PGE(2) production of C2 cultured in DEH-AA is the consequence of the AA enrichment, because AA is the precursor of PGE(2). However, the different effects by AA and EPA on mast cell mediators possibly reflect the higher susceptibility of long chain polyunsaturated fatty acids (PUFA) to undergo lipid peroxidation, because it is known that altered cellular redox state influences mediator production and release.