The biosynthetic activity of cyclooxygenase and lipoxygenase (ex soya) requires lipid peroxide to initiate the fatty acid oxygenation. This research project examines the ratio of peroxide-generating to peroxide-removing activity in cells to assess the extent to which leukocytes and their hydroperoxide products enhance the biosynthesis of prostaglandins and leukotrienes. Experiments will be designed to: 1) examine the stimulating activity of hydroperoxides on mammalian 5-lipoxygenase in the presence and absence of glytathione peroxidase; 2) identify the oxygenase stimulating material derived from leukocytes in the presence and absence of superoxide dismutase of catalase; 3) develop a quantitative assay for nanomolar amounts of hydroperoxide; 4) measure the increase in cellular and extracellular oxygenase products following different types of stimulation of leukocytes; 5) peroxidase on controlling cyclooxygenase production of prostaglandins and lipoxygenase production of leukotrienes; 6) interpret the actions of antioxidant radical scavenger agents upon the fatty acid oxygenase activities of intact cells; 7) examine the degree to which cell-cell signalling can affect the formation of prostaglandins or leukotrienes; 8) compare the kinetic features of cyclooxygenase activity from different leukocytes. Normal and elicited preparations of neutrophils and macrophages from guinea pigs will be separated by gradient centrifugation. The cells will be tested for their ability to generate materials that can stimulate the consumption of oxygen or the formation of radioactive arachindonate products by cellular and cell-free fatty acid oxygenase systems. Our results will provide new insights into the mechanism of inflammation and provide a constructive rationale for the development of new therapeutic anti-inflammatory agents.
| Marshall, P J; Kulmacz, R J; Lands, W E (1987) Constraints on prostaglandin biosynthesis in tissues. J Biol Chem 262:3510-7 |
| Lands, W E; Miller Jr, J F; Rich, S (1987) Influence of dietary fish oil on plasma lipid hydroperoxides. Adv Prostaglandin Thromboxane Leukot Res 17B:876-9 |
| Marshall, P J; Lands, W E (1986) In vitro formation of activators for prostaglandin synthesis by neutrophils and macrophages from humans and guinea pigs. J Lab Clin Med 108:525-34 |
| Lands, W E; Kulmacz, R J (1986) The regulation of the biosynthesis of prostaglandins and leukotrienes. Prog Lipid Res 25:105-9 |
| Warso, M A; Lands, W E (1985) Presence of lipid hydroperoxide in human plasma. J Clin Invest 75:667-71 |
| Lands, W E; Marshall, P J; Kulmacz, R J (1985) Hydroperoxide availability in the regulation of the arachidonate cascade. Adv Prostaglandin Thromboxane Leukot Res 15:233-5 |
| Marshall, P J; Warso, M A; Lands, W E (1985) Selective microdetermination of lipid hydroperoxides. Anal Biochem 145:192-9 |
| Lands, W E (1985) Interactions of lipid hydroperoxides with eicosanoid biosynthesis. J Free Radic Biol Med 1:97-101 |
