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

• DOI: 10.1194/jlr.m800574-jlr200
• Publication Date: 2009-03-18T02:43:16Z
• Authors: Tsong-Long Hwang; Yi-Chia Su; Han-Lin Chang; Yann-Lii Leu; Pei-Jen Chung; Liang-Mou Kuo; Yi-Ju Chang
• Keywords: Adult; Neutrophils; QD415-436; Calcium-Transporting ATPases; Biochemistry; Structure-Activity Relationship; Young Adult; 03 medical and health sciences; plasma membrane Ca2+-ATPase; Superoxides; cAMP; Cyclic AMP; Humans; Enzyme Inhibitors; Protein Kinase C; 0303 health sciences; calcium; Pancreatic Elastase; structure-activity relationship; 3. Good health; N-Formylmethionine Leucyl-Phenylalanine; Barium; Fatty Acids, Unsaturated; Thapsigargin; Calcium

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