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

AUTOR(ES)

Hwang, Tsong-Long

FONTE

American Society for Biochemistry and Molecular Biology

RESUMO

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.

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