Heiskanen K M, Savolainen K M
National Public Health Institute, Department of Toxicology, Kuopio, Finland.
Toxicology. 1996 Jun 17;110(1-3):39-45. doi: 10.1016/0300-483x(96)03320-3.
Linoleic and oleic acid anilides profoundly inhibited the production of reactive oxygen metabolites (ROM) in human polymorphonuclear leukocytes (PMNL) induced by a tumor promoter, phorbol myristate acetate (PMA). The addition of a Ca2+ ionophore, A23187, or a chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (fMLP), readily reversed linoleic and oleic acid anilide-induced inhibiton of PMA-evoked respiratory burst in PMNL without affecting PMA-induced respiratory burst. fMLP or A23187 caused a marked increase in the production of ROM in PMNL that did not produce ROM after their co-exposure to PMA and cis-fatty acid anilides. This suggests a role for Ca2+ in this restoration of respiratory burst activity in PMNL. Oleic and linoleic acid anilides enhanced also respiratory burst in PMNL subsequent to their stimulation with fMLP. Interestingly, corresponding fatty acids, linoleic and oleic acid, also inhibited PMA-induced production of ROM in PMNL, but this inhibition was not reversed by A23187 or fMLP. These findings suggest that the aniline moiety of cis-fatty acids significantly modifies the effects of linoleic and oleic acids in the production of ROM in PMNL. Moreover, free intracellular Ca2+ may play a critical role in the activation of PMNL to produce ROM, and in the modulation of the effects of cis-fatty acid anilides.
亚油酸和油酸苯胺对肿瘤启动子佛波酯（PMA）诱导的人多形核白细胞（PMNL）中活性氧代谢产物（ROM）的产生有显著抑制作用。添加钙离子载体A23187或趋化肽甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP），可轻易逆转亚油酸和油酸苯胺对PMA诱导的PMNL呼吸爆发的抑制作用，且不影响PMA诱导的呼吸爆发。fMLP或A23187可使与PMA和顺式脂肪酸苯胺共同孵育后不产生ROM的PMNL中的ROM生成显著增加。这表明钙离子在PMNL呼吸爆发活性的恢复中起作用。油酸和亚油酸苯胺在fMLP刺激后也增强了PMNL的呼吸爆发。有趣的是，相应的脂肪酸亚油酸和油酸也抑制PMA诱导的PMNL中ROM的产生，但这种抑制作用不能被A23187或fMLP逆转。这些发现表明顺式脂肪酸的苯胺部分显著改变了亚油酸和油酸在PMNL中ROM产生方面的作用。此外，细胞内游离钙离子可能在激活PMNL产生ROM以及调节顺式脂肪酸苯胺的作用中起关键作用。
