Unsaturated fatty acids stimulate NADPH-dependent superoxide production by cell-free system derived from macrophages.
Arachidonic acid (C20:4) and other unsaturated fatty acids are shown to activate superoxide (O2-) production in a cell-free system represented by sonically disrupted guinea pig peritoneal macrophages. The reaction requires a heat-sensitive cellular component and NADPH, is enhanced by flavin adenine dinucleotide (FAD), and is not linked to enzymatic oxidation of the fatty acid. C20:4-elicited O2- formation is dependent on the cooperation between a subcellular component sedimentable at 48,000g (probably containing the O2- -forming enzyme) and a cytosolic factor. This appears to be the first report of O2- generation being elicited in a cell-free system derived from unstimulated cells and supports the idea that unesterified unsaturated fatty acids act as second messengers of O2- formation in intact phagocytes.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002474:Cell-Free System; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006168:Guinea Pigs; D007700:Kinetics; D008264:Macrophages / Q000502:physiology*; D009249:NADP / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D013481:Superoxides / Q000096:biosynthesis*
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D013481:Superoxides; D005182:Flavin-Adenine Dinucleotide; D016718:Arachidonic Acid; D009249:NADP; D002118:Calcium