5-hydroxy-6-8-11-14-eicosatetraenoic-acid and 12-hydroxy-5-8-10-heptadecatrienoic-acid

Type I hypersensitivity is an immediate immune reaction that involves IgE-mediated activation of mast cells. Activated mast cells release chemical mediators, such as histamine and lipid mediators, which cause allergic reactions. Recent developments in detection devices have revealed that mast cells simultaneously release a wide variety of lipid mediators. Mounting evidence has revealed that mast cell-derived mediators exert both pro- and anti-inflammatory functions and positively and negatively regulate the development of allergic inflammation. This review presents the roles of major lipid mediators released from mast cells. Author believes this review will be helpful for a better understanding of the pathogenesis of allergic diseases and provide a new strategy for the diagnosis and treatment of allergic reactions.

Topics: Fatty Acids, Unsaturated; Histamine Release; Humans; Hydroxyeicosatetraenoic Acids; Hypersensitivity, Immediate; Immunoglobulin E; Inflammation; Leukotriene B4; Leukotriene C4; Lipid Metabolism; Mast Cells; Prostaglandin D2

As a Chinese traditional herbal medicine, leaves of Platycladus orientalis (Linnaeus) Franco (LPO) are used to treat coughs, excessive mucus secretion, chronic bronchitis, bronchiectasis, and asthma, etc. The experiments were carried out to investigate their anti-inflammatory properties and mechanisms, which could support the Chinese traditional uses of treating inflammatory airway diseases.. The anti-inflammatory activities of the chloroform fraction (CHL) and pure compounds of LPO were evaluated for their abilities to inhibit pro-inflammatory enzymes in vitro, and production of tumor necrosis factor-α (TNF-α) and nitric oxide in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Furthermore, the arachidonic acid metabolites, stimulated by calcium ionophore A23187, were also determined by HPLC.. For the first time, the assays of eicosanoids in intact cells showed that the CHL, hinokiol, and acacetin had significant inhibitory effects on 5-hydroxy-eicosa-tetra-enoic acid (5-HETE) and leukotriene B(4) (LTB4) formations. And cell-free enzyme assays (5-lipoxygenase, leukotriene A(4)-hydrolase, cyclooxgenase-2) demonstrated the potent inhibitory effects of the CHL, hinokiol and acacetin on 5-lipoxygenase (5-LOX). Then, the inhibitions of the CHL, hinokiol on NO biosynthesis and the inhibitions of the CHL, 8(14),15-pimaradien-3β,18-diol, and hinokiol on TNF-α release were also confirmed in the RAW264.7 murine macrophages.. The data indicate that the inhibitory effects of the CHL and its components (hinokiol and acacetin) on 5-LOX contribute to the anti-inflammatory activity of LPO. Moreover, the CHL and its components also show beneficial effects on NO and TNF-α production. Consequently, these results provide a rationale for LPO's traditional applications in the treatment of inflammatory airway diseases.

Topics: Animals; Anti-Inflammatory Agents; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Calcimycin; Calcium Ionophores; Cell Line; Chloroform; Chromatography, High Pressure Liquid; Cupressaceae; Cyclooxygenase 2; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Epoxide Hydrolases; Fatty Acids, Unsaturated; Flavones; Hydroxyeicosatetraenoic Acids; Inflammation Mediators; Leukotriene B4; Lipoxygenase Inhibitors; Macrophages; Medicine, Chinese Traditional; Mice; Nitric Oxide; Plant Leaves; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Solvents; Tumor Necrosis Factor-alpha

Recent studies have shown that long-term in vivo exposure of dogs to neutral sulfur(IV)/sulfite aerosols induces mild inflammatory reactions, whereas the combination of neutral sulfite with acidic sulfur(VI)/sulfate aerosols evokes less pronounced effects. To understand underlying mechanisms, we studied in vitro the role of lipid mediators in the responses of alveolar macrophages (AMs) to sulfur-related compounds under neutral (pH 7) or moderate acidic (pH 6) conditions. Canine AMs incubated with sulfite at pH 7 released threefold higher amounts of platelet-activating factor than control (P < 0.005). Generation of arachidonic acid, leukotriene B4, 5-hydroxy-eicosatetraenoic acid, prostaglandin E2, thromboxane B2 and 12-hydroxyheptadecatrienoic acid increased twofold (P < 0.0005). However, these metabolites remained unchanged following incubation of AMs with sulfite at pH 6 or with sulfate at pH 7 or pH 6. Mediator release by sulfite-treated AMs at pH 7 stimulated respiratory burst activity of neutrophils. Inhibition of MAPK pathway by PD 98059, of cytosolic (cPLA2) and secretory phospholipases A2 by AACOCF3 and thioetheramide-PC, respectively, reduced sulfite-induced eicosanoid formation in AMs. Sulfite activated cPLA2 activity twofold at pH 7. This mechanism of sulfite-stimulated responses in phospholipid metabolism predicts that chronic exposure to sulfur(IV)/sulfite is associated with a considerable health risk.

Topics: Air Pollutants; Animals; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Autoradiography; Carbon Radioisotopes; Cells, Cultured; Chromatography, Thin Layer; Dinoprostone; Dogs; Enzyme Activation; Fatty Acids, Unsaturated; Hydrogen-Ion Concentration; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Macrophages, Alveolar; Phospholipases A; Platelet Activating Factor; Prostaglandin-Endoperoxide Synthases; Sulfates; Sulfites; Sulfur; Thromboxane B2

Studies were made on the effects of stilbene derivatives isolated from medicinal plants on arachidonate metabolism and degranulation in human polymorphonuclear leukocytes (PMN-L). Resveratrol (3,4',5-trihydroxystilbene) isolated from the roots of Reynoutria japonica was found to inhibit the 5-lipoxygenase products 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE), 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid (5,12-diHETE) and leukotriene C4(LTC4); its concentrations for 50% inhibition (IC50) were 8.90 x 10(-6) M, 6.70 x 10(-6) M and 1.37 x 10(-6) M, respectively. The IC50 of 5-HETE, 5,12-diHETE and LTC4 formations of synthetic 3,3',4-trihydroxystilbene were 5.90 x 10(-6) M, 6.30 x 10(-7) M and 8.80 x 10(-7) M, respectively. Moreover, they inhibited the release of lysosomal enzyme such as lysozyme and beta-glucuronidase induced by calcium ionophore A 23187 from human PMN-L at 10(-3)-10(-4) M.

Topics: Arachidonic Acid; Autoradiography; Calcimycin; Cell Degranulation; Cyclic AMP; Fatty Acids, Unsaturated; Glucuronidase; Humans; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Leukotriene C4; Lysosomes; Muramidase; Neutrophils; Plant Roots; Plants, Medicinal; Resveratrol; Stilbenes; Structure-Activity Relationship

Density-defined macrophages isolated from fluids of patients with liver cirrhosis mainly generated the 5-lipoxygenase products leukotriene B4 (LTB4, 16%) and 5-hydroxy-eicosatetraenoic acid (5-HETE, 24%) and the cyclooxygenase products 12-hydroxyheptadecatrienoic acid (HHT, 22%) and thromboxane B2 (TXB2, 18%). The synthesis of eicosanoids was linear with the maturity of the macrophage subpopulations, suggesting that eicosanoid production is increased in in-vivo activated macrophages.

Topics: Eicosanoids; Fatty Acids, Unsaturated; Humans; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Lipoxygenase; Liver Cirrhosis; Macrophages; Peritoneal Cavity; Prostaglandin-Endoperoxide Synthases; Thromboxane B2

Inhibition of 5-lipoxygenase has been determined by monitoring the formation of leukotriene B4 and 5-hydroxyeicosatetraenoic acid in bovine polymorphonuclear leucocytes. For evaluating the inhibition of cyclo-oxygenase two different test systems are presented: the first uses 12-hydroxyheptadecatrienoic acid produced by bovine platelets as an indicator of the cyclo-oxygenase activity; the second test system monitors the prostaglandin E2 formation by bovine platelets. All arachidonic acid metabolites are quantified by reverse-phase HPLC with UV-detection.

Topics: Animals; Blood Platelets; Cattle; Chromatography, High Pressure Liquid; Cyclooxygenase Inhibitors; Dinoprostone; Fatty Acids, Unsaturated; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Kinetics; Leukotriene B4; Lipoxygenase Inhibitors; Neutrophils; Spectrophotometry, Ultraviolet

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Arachidonic Acid; Arachidonic Acids; Chromatography, High Pressure Liquid; Dinoprostone; Fatty Acids, Unsaturated; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Lipoxygenase; Male; Neutrophils; Peritoneal Cavity; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Inbred Lew; Thromboxane B2

The in vitro release of arachidonic acid (AA) metabolites from caprine alveolar macrophages (CAM) stimulated with the calcium ionophore A23187 or opsonized zymosan was examined. Leukotriene B4 [5(S),12(R)-6,14-cis-8,10-trans-dihydroxyeicosatetraenoic acid] was the major AA metabolite elicited with either agonist; smaller amounts of 12- and 5-mono-hydroxyeicosatetraenoic acid (HETE), and 12-hydroxyheptadecatrienoic acid (HHT) were also detected. Zymosan stimulation also caused the release of very small quantities of prostaglandins E2 and F2 alpha, and thromboxane B2. Our report is the first to describe arachidonic acid metabolism in CAM.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Arachidonic Acid; Arachidonic Acids; Bronchoalveolar Lavage Fluid; Calcimycin; Fatty Acids, Unsaturated; Goats; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Lipid Metabolism; Macrophages; Zymosan

Topics: Animals; Arachidonic Acids; Fatty Acids, Unsaturated; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Male; Neutrophils; Pleura; Rats; Rats, Inbred Strains; Solanaceous Alkaloids; Thromboxane B2

12-Hydroxyheptadecatrienoic acid (HHT), a UV chromophore, has been used to assess cyclooxygenase (CO) pathway metabolism of arachidonic acid (AA) by rat peritoneal cells. Simultaneous monitoring at 235 and 280 nm after HPLC permits the measurement of both CO and 5-lipoxygenase (5-LO) pathway fluxes in a single system.

Topics: Animals; Arachidonate 5-Lipoxygenase; Arachidonic Acids; Ascitic Fluid; Calcimycin; Chromatography, High Pressure Liquid; Cyclooxygenase Inhibitors; Eosinophils; Fatty Acids, Unsaturated; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Lipoxygenase Inhibitors; Macrophages; Male; Mast Cells; Prostaglandin Antagonists; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Inbred Strains; Reference Standards; Spectrophotometry, Ultraviolet

A stable isotope dilution gas chromatography-negative ion chemical ionization-mass spectrometry assay for simultaneous quantitative measurement of 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE, 15-HETE, and 12-hydroxyheptadecatrienoic acid in one single GC/MS run was established. 18O2-Labeled analogs as internal standards, prepared according to conventional procedures, were found to be useful for this application. A sample processing and derivatization sequence providing highly purified compounds with a recovery of 42.7% was elaborated. The detection limit was in the femtomole range.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Fatty Acids, Unsaturated; Gas Chromatography-Mass Spectrometry; Hydroxyeicosatetraenoic Acids; Indicator Dilution Techniques; Isotope Labeling; Oxygen Isotopes

The effects of various alpha-phenylcinnamic acid derivatives (i.e., alpha-(3,4-dihydroxyphenyl)cinnamic acid, alpha-(3,4-dihydroxyphenyl)-3-hydroxycinnamic acid, alpha-(3,4-dihydroxyphenyl)-4-hydroxycinnamic acid and alpha-(3,4-dihydroxyphenyl)-3, 4-dihydroxycinnamic acid) synthesized from 3,4-dihydroxyphenyl acetic acid and hydroxy-benzaldehyde, and 3,3',4-trihydroxystilbene obtained by decarboxylation of alpha-(3,4-dihydroxyphenyl)-3-hydroxycinnamic acid on rat peritoneal polymorphonuclear leukocyte lipoxygenase and cyclooxygenase activities were studied. 3,3',4-Trihydroxystilbene was found to inhibit the 5-lipoxygenase product, 5-hydroperoxy-6,8,11,14-eicosatetraenoic acid (5-HETE), and cyclooxygenase products, 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and thromboxane B2; its concentrations for 50% inhibition (IC50) were 0.885 +/- 0.016 microM for the leukocyte lipoxygenase product, 5-HETE, 7.70 +/- 0.104 microM for the formations of HHT and 7.96 +/- 0.143 microM for the formation of thromboxane B2. Alpha-(3,4-Dihydroxyphenyl)cinnamic acid, alpha-(3,4-dihydroxyphenyl)-3-hydroxycinnamic acid and alpha-(3,4-dihydroxyphenyl)-3,4-dihydroxycinnamic acid also inhibited the formations of 5-HETE, HHT and thromboxane B2, although less strongly. Their IC50 values were, respectively, 91.3 +/- 3.62 microM, 947.5 +/- 28.7 microM, 453.3 +/- 229.3 microM and 148.8 +/- 50.6 microM for the formation of 5-HETE, 894.0 +/- 5.57 microM, 792.5 +/- 15.9 microM, greater than 1000 microM and 925.0 +/- 7.64 microM for the formation of HHT and 941.0 +/- 18.0 microM, 825 +/- 14.4 microM, greater than 1000 microM and 932.7 +/- 3.93 microM for the formation of thromboxane B2.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Dose-Response Relationship, Drug; Fatty Acids, Unsaturated; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Leukocytes; Rats; Stilbenes; Thromboxane B2

Normal hemostasis depends in part on the balance achieved between proaggregatory and prothrombotic platelet thromboxane A2, measured as its stable end-product thromboxane B2 (TXB2), and vascular prostacyclin (PGI2), which inhibits platelet aggregation and is antithrombotic. Cystathionine-beta-synthase deficiency is characterized by a high frequency of thromboembolic disease. We therefore studied, in vitro, the effects of homocysteine and related compounds on platelet TXB2 and vascular PGI2 formation. In paired samples of platelet rich plasma, which had been preincubated with L-homocystine (1 mM), mean production of the two platelet cyclooxygenase products, TXB2 and 12-hydroxy-5, 8,10-heptadecatrienoic acid increased significantly from control levels [13.6% +/- 1.9 to 19.8% +/- 2.1 (P less than 0.02) TXB2 and 29.8% +/- 4.2 to 39.4% +/- 4.1 (P less than 0.01) HHT]. In the presence of D,L-homocysteine (1 mM), mean TXB2 and 12-hydroxy-5,8,10-heptadecatrienoic acid production was also significantly increased [12.7% +/- 1.5 to 16.9% +/- 1.5 (P less than 0.01) TXB2 and 27% +/- 4 to 31% +/- 4.1 (P less than 0.02) HHT]. Cystine, cysteine, or methionine (1 mM) did not have similar effects in this test system. Homocysteine and homocystine were without effect on the synthesis of vascular PGI2 by umbilical artery segments [control, 0.22 +/- 0.03 to 0.21 +/- 0.03 ng/mg with D,L-homocysteine and 0.20 +/- 0.04 control to 0.19 +/- 0.04 ng/mg with D,L-homocystine]. A homocyst(e)ine-induced increase in platelet thromboxane production in the absence of an increase in vascular prostacyclin, if present in vivo, may contribute to the vascular thromboses characteristic of human homocystinemias (homocystinurias).

Topics: Arachidonic Acid; Arachidonic Acids; Blood Platelets; Epoprostenol; Fatty Acids, Unsaturated; Homocysteine; Homocystine; Humans; Hydroxy Acids; Hydroxyeicosatetraenoic Acids; Methionine; Thromboxane A2; Umbilical Arteries

Rat neutrophils isolated from three-hour carrageenan pleural exudates actively metabolize arachidonic acid into three major metabolites, HHT, 11-HETE and 15-HETE. However, in the presence of the calcium ionophore, A23187, or the non-ionic detergent, BRIJ 56, these cells also produce 5-HETE and LTB. The production of these lipoxygenase products is calcium dependent. While non-steroidal anti-inflammatory drugs do not affect 5-HETE or LTB production, BW 755C and ETYA inhibit formation of these metabolites from exogenously added arachidonic acid.

Topics: Animals; Arachidonic Acids; Calcimycin; Carrageenan; Cetomacrogol; Exudates and Transudates; Fatty Acids, Unsaturated; Hydroxy Acids; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Lipoxygenase; Male; Neutrophils; Pleura; Rats