Prostaglandins and leukotrienes

Abstract

The eicosanoids are a group of substances with wideranging biological activities which are produced in cells from polyunsaturated fatty acids, particularly arachidonic acid (AA). The enzymes initially involved in the production of eicosanoids and their primary products are a cyclooxygenase, which forms prostaglandin (PG) eridoperoxides, and the various lipoxygenases, which form hydroperoxy fatty acids [l] (Parker, Annu Reu Zmmunol 1987, 6:65-84; Samuelsson et al., Science 1987, 237:1171-1175). The cyclooxygenase product& PGs, thromboxanes and prostacyclin (PGIz) aker smooth muscle tone, vascular permeability, platelet adhesiveness, and lymphocyte function. The lipoxygenase products, leukotriene (LT)&, LTB4, LTC4, LTD4, LTE4, and long-chain hydroperoxides (HPETEs) and hydroxyacids (HETEs) increase cell aggregation, chemotaxis, secretion, vascular permeability and smooth muscle contractility (Parker. In Fundamental Immunology edited by Paul. Raven Press, 1984, pp 697-747). Another pathway of AA metabolism is cytochrome P450-dependent oxidation that produces 5,6and other epoxides (Pickett et al., Biocbim B@bys Acts 1987, 486:209-213; Proctor et al, Circ Res 1987, 6050-59). The 5,6-epoxide of AA bas significant vasodilator activity and may also be capable of stimulating secretion. The cyclooxygenase and lipoxygenase enzymes may have roles in immune regulation other than the production of vasoactive and chemotactic mediators. Many of the effects of interleukin (IL)-1 and tumor necrosis factor appear to be media& via local effects on AA metabolism (Parker. In Allergy, Theory and Practice edited by Korenblat and Wedner. Grune-Stratton, 1984, pp 25-39).