In vitro effects of Ω-3 fatty acids on neutrophil intracellular calcium homeostasis and receptor expression for FMLP and LTB₄

Abstract

Diets enriched inΩ-3 fatty acids exert antiinflammatory properties by suppressing some neutrophil (PMN) functions. Changes in cytosolic Ca²⁺ concentration, [Ca²⁺]_i, are important for PMN activation and are in part regulated by membrane Ca²⁺ ATPases. Since membrane proteins are influenced by their lipid environment, we investigated the in vitro effects of theΩ-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the [Ca²⁺]_i of PMNs in response to f-Met-LeuPhe (FMLP), leukotriene B₄ (LTB₄), and ionomycin. The resting [Ca²⁺]_i of PMNs (in high Ca²⁺ environment) was increased after pretreatment (37‡C, 2 h) with DHA, but not with EPA, or the other fatty acids, oleic acid (OA), or linolenic acid (LA). The stimulated [Ca²⁺]_i by either FMLP or LTB₄ was suppressed in a high Ca²⁺ environment after pretreatment with either EPA or DHA but not with OA or LA. The stimulated [Ca²⁺]_i rise by ionomycin was augmented after pretreatment with DHA but not with EPA, OA, or LA. Pretreatment of PMNs with either EPA or DHA reduced the receptor expression for both FMLP and LTB₄. Since Ω-3 fatty acids inhibit the expression of receptors for two activators of PMNs, FMLP and LTB₄, as well as the [Ca²⁺]_i rise in response to those two stimuli, we propose that the antiinflammatory properties of EPA and DHA may be attributed, at least in part, to alteration in membrane activation of phagocytes.