Suppression of superoxide anion and elastase release by C18 unsaturated fatty acids in human neutrophils

摘要

The structure-activity relationship of 18-carbon fatty acids (C18 FAs) on human neutrophil functions and their underlying mechanism were investigated. C18 unsaturated (U)FAs potently inhibited superoxide anion production, elastase release, and Ca²⁺ mobilization at concentrations of <10 μM in formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP)-activated human neutrophils. However, neither saturated FA nor esterified UFAs inhibited these neutrophil functions. The inhibitory potencies of C18 UFAs decreased in the following order: C18:1 > C18:2 > C18:3 > C18:4. Notably, the potency of attenuating Ca²⁺ mobilization was closely correlated with decreasing cellular responses. The inhibitions of Ca²⁺ mobilization by C18 UFAs were not altered in a Ca²⁺-containing Na⁺-deprived medium. Significantly, C18 UFAs increased the activities of plasma membrane Ca²⁺-ATPase (PMCA) in neutrophils and isolated cell membranes. In contrast, C18 UFAs failed to alter either the cAMP level or phosphodiesterase activity. Moreover, C18 UFAs did not reduce extracellular Ba²⁺ entry in FMLP- and thapsigargin-activated neutrophils. In summary, the inhibition of neutrophil functions by C18 UFAs is attributed to the blockade of Ca²⁺ mobilization through modulation of PMCA. We also suggest that both the free carboxy group and the number of double bonds of the C18 UFA structure are critical to providing the potent anti-inflammatory properties in human neutrophils.