Abstract
Gammalinolenic acid (GLA; 18:3n6) and dihomogammalinolenic acid (DGLA; 20:3n6) suppress lymphocyte activation, and GLA administration reduces joint swelling and tenderness in rheumatoid arthritis patients with active synovitis. In an effort to dissect the mechanisms whereby GLA, DGLA, and other fatty acids influence lymphocyte function, we examined their effects on anti-CD3 monoclonal antibody (mAb)-mediated early signaling events in human T cells. Peripheral blood mononuclear cells from healthy individuals were incubated overnight at 37 degrees C with or without 10 microg/ml fatty acid and then loaded with the calcium binding fluorescent dye indo-1. Fatty acids did not affect the efficiency of indo-1 loading, and they did not alter cell surface membrane expression of the CD3 molecule. Anti-CD3 mAb (G19-4)-induced intracellular calcium [(Ca2+)i] changes were monitored by flow cytometry in negatively selected human T cells. The ratio of violet to blue fluorescence, which is proportional to (Ca2+)i, was measured over time. Cells enriched with GLA and DGLA but not cells enriched with eicosapentaenoic acid (20:5n3) displayed a significant reduction in anti-CD3 mAb-induced early and late (Ca2+)i responses. T cells loaded with GLA, D...Continue Reading
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