Arachidonic acid triggers an oxidative burst in leukocytes

Abstract

The change in cellular reducing potential, most likely reflecting an oxidative burst, was investigated in arachidonic acid-(AA) stimulated leukocytes. The cells studied included the human leukemia cell lines HL-60 (undifferentiated and differentiated into macrophage-like and polymorphonuclear-like cells), Jurkat and Raji, and thymocytes and macrophages from rat primary cultures. The oxidative burst was assessed by nitroblue tetrazolium reduction. AA increased the oxidative burst until an optimum AA concentration was reached and the burst decreased thereafter. In the leukemia cell lines, optimum concentration ranged from 200 to 400 µM (up to 16-fold), whereas in rat cells it varied from 10 to 20 µM. Initial rates of superoxide generation were high, decreasing steadily and ceasing about 2 h post-treatment. The continuous presence of AA was not needed to stimulate superoxide generation. It seems that the NADPH oxidase system participates in AA-stimulated superoxide production in these cells since the oxidative burst was stimulated by NADPH and inhibited by Nethylmaleimide, diphenyleneiodonium and superoxide dismutase. Some of the effects of AA on the oxidative burst may be due to its detergent action. There apparently was no contribution of other superoxide-generating systems such as xanthine-xanthine oxidase, cytochromes P-450 and mitochondrial electron transport chain, as assessed by the use of inhibitors. Eicosanoids and nitric oxide also do not seem to interfere with the AA-stimulated oxidative burst since there was no systematic effect of cyclooxygenase, lipoxygenase or nitric oxide synthase inhibitors, but lipid peroxides may play a role, as indicated by the inhibition of nitroblue tetrazolium reduction promoted by tocopherol.

Fatty acids decrease catalase activity in human leukaemia cell lines

“…In phagocytes, AA stimulates superoxide generation, being cytotoxic at physiological and supraphysiological concentrations. 33,34 In addition to stimulating ROS production, 35 the present study provides evidence that FA also decreases the activitiy of catalase in Jurkat and Raji cells. FAs, mainly the PUFAs ones, are also putative targets for free radical propagation, during which lipid peroxides are generated, being deleterious for the tissues.…”

Interactions between Nitric Oxide and Arachidonic Acid in Lung Epithelial Cells: Possible Roles for Peroxynitrite and Superoxide

“…An elevation in superoxide generation increases NOS activity and mRNA levels [34]. Additional studies have shown that the AA release was accompanied by an increased superoxide formation [35,36] and that the PLA 2 inhibitor AACOCF 3 was capable of reducing superoxide formation [36,37]. Therefore, it can be hypothesized that the reduction in nitrite formation following exposure to AACOCF 3 may be mediated by lower levels of superoxide.…”

Twisting of the spermatic cord: ischemia and reperfusion, toxicogenetic evaluation, and the effects of phosphatidylcholine in pre-clinical trials

“…Its metabolites are important mediators of intracellular signaling (Cui and Houweling, 2002), inflammation (Pompéia et al, 2003), and immunomodulation (Courrèges et al, 2003). It has also been reported that phosphatidylcholine increases the solubility of cholesterol and can therefore change the composition of fatty deposits and inhibit platelet aggregation, reducing the risk of cardiovascular disease (Mel'Chinskaia et al, 2000).…”