prostaglandin-d2 and 5-hydroxy-6-8-11-14-eicosatetraenoic-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

The 2 hemiketal (HK) eicosanoids HKD

Topics: Arachidonate 5-Lipoxygenase; Arachidonic Acid; Blood Platelets; Calcimycin; Cyclooxygenase 2; Dinoprostone; Humans; Hydroxyeicosatetraenoic Acids; Leukocytes; Prostaglandin D2

MDA-MB-231, MCF7, and SKOV3 cancer cells, but not HEK-293 cells, expressed mRNA for the leukocyte G protein-coupled 5-oxo-eicosatetraenoate (ETE) OXE receptor. 5-Oxo-ETE, 5-oxo-15-OH-ETE, and 5-HETE stimulated the cancer cell lines but not HEK-293 cells to mount pertussis toxin-sensitive proliferation responses. Their potencies in eliciting this response were similar to their known potencies in activating leukocytes and OXE receptor-transfected cells. However, high concentrations of 5-oxo-ETE and 5-oxo-15-OH-ETE, but not 5-HETE, arrested growth and caused apoptosis in all four cell lines; these responses were pertussis toxin-resistant. The same high concentrations of the oxo-ETEs but again not 5-HETE also activated peroxisome proliferator-activated receptor (PPAR)-gamma. Pharmacological studies indicated that this activation did not mediate their effects on proliferation. These results are the first to implicate the OXE receptor in malignant cell growth and to show that 5-oxo-ETEs activate cell death programs as well as PPARgamma independently of this receptor.

Topics: Anilides; Apoptosis; Arachidonic Acids; Binding Sites; Caspase 3; Caspases; Cell Line; Cell Line, Tumor; Cell Proliferation; Cell Survival; Gene Expression; Humans; Hydroxyeicosatetraenoic Acids; Mitosis; Peroxisome Proliferator-Activated Receptors; Pertussis Toxin; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; PPAR gamma; Prostaglandin D2; Protein Binding; Receptors, Eicosanoid; Transfection

Capsaicin, a pungent ingredient of hot peppers, causes excitation of small sensory neurons, and thereby produces severe pain. A nonselective cation channel activated by capsaicin has been identified in sensory neurons and a cDNA encoding the channel has been cloned recently. However, an endogenous activator of the receptor has not yet been found. In this study, we show that several products of lipoxygenases directly activate the capsaicin-activated channel in isolated membrane patches of sensory neurons. Among them, 12- and 15-(S)-hydroperoxyeicosatetraenoic acids, 5- and 15-(S)-hydroxyeicosatetraenoic acids, and leukotriene B(4) possessed the highest potency. The eicosanoids also activated the cloned capsaicin receptor (VR1) expressed in HEK cells. Prostaglandins and unsaturated fatty acids failed to activate the channel. These results suggest a novel signaling mechanism underlying the pain sensory transduction.

Topics: Animals; Capsaicin; Cell Line; Cells, Cultured; Dinoprostone; Eicosanoids; Ganglia, Spinal; Humans; Hydroxyeicosatetraenoic Acids; Inflammation; Ion Channel Gating; Leukotriene B4; Leukotrienes; Ligands; Lipid Peroxides; Lipoxygenase; Molecular Structure; Neurons, Afferent; Prostaglandin D2; Prostaglandin H2; Prostaglandins H; Rats; Receptors, Drug; Structure-Activity Relationship

Topics: Animals; Arachidonate 5-Lipoxygenase; Butyrates; Butyric Acid; Hydroxyeicosatetraenoic Acids; Leukemia, Basophilic, Acute; Prostaglandin D2; Prostaglandin-Endoperoxide Synthases; Rats; Tumor Cells, Cultured

Recent evidence has shown that a variety of prostaglandins and leukotrienes can be produced in brain tissue after injury in animals. It has also been speculated that increases in brain prostaglandins occur in humans following injury. Ventricular cerebrospinal fluid (CSF) samples have been obtained from children with static lesions (controls) as well as children with acute brain injury and eicosanoids measured by immunologic techniques. Metabolites of prostacyclin (6-keto-PGF1 a) and thromboxane A2 (thromboxane B2) were the major eicosanoids found in CSF, and levels of these compounds were increased 3-10 times in acutely injured patients. Prostaglandin E2 was also found in lower amounts, although in one case its level was very high. Prostaglandin D2 was also present, but in low amounts. No leukotrienes were found in CSF samples that were purified by HPLC prior to immunoassay. Elevated levels of hydroxyeicosatetraenoic acids (HETEs) were observed in those samples stored frozen, but these metabolites were most probably due to autooxidation of arachidonic acid in CSF. Arachidonic acid concentration in CSF was typically found to be in the range of 10-200 ng/ml, but was found to be 5-10 fold higher in one severely injured patient. Thus, elevated free arachidonic acid and various oxygenated metabolites were observed in CSF following brain injury.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 6-Ketoprostaglandin F1 alpha; Adolescent; Arachidonic Acid; Arachidonic Acids; Brain Injuries; Cerebral Ventricles; Child; Child, Preschool; Chromatography, High Pressure Liquid; Dinoprostone; Eicosanoic Acids; Humans; Hydroxyeicosatetraenoic Acids; Infant; Infant, Newborn; Leukotriene B4; Prostaglandin D2; Prostaglandins D; Prostaglandins E; SRS-A; Thromboxane B2

The effects of alcohols on the formation of leukotrienes, 5-HETE and prostaglandin D2 in mastocytoma cells and human neutrophils were studied. In murine mastocytoma cells, alcohols appear to have at least two different effects on the production of these arachidonic acid metabolites. At low levels of cellular arachidonic acid achieved after stimulation with calcium ionophore A23187 or addition of low levels of exogenous arachidonic acid, alcohols appear to have a general inhibitory effect on the production of lipoxygenase metabolites. In the presence of higher concentrations of cellular arachidonic acid, ethanol and methanol stimulated the production of lipoxygenase metabolites, but had no large stimulatory effect on the cyclo-oxygenase metabolite, prostaglandin D2. Under these conditions, n-propanol and t-butanol have inhibitory effects on leukotriene production. Human neutrophils are less sensitive to ethanol than mastocytoma cells, but stimulatory effects were still found at high ethanol concentrations (220-430 mM).

Topics: Alcohols; Animals; Arachidonic Acid; Arachidonic Acids; Calcimycin; Cell Line; Cell-Free System; Chromatography, High Pressure Liquid; Ethanol; Humans; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Lipoxygenase; Mast-Cell Sarcoma; Methanol; Mice; Neutrophils; Prostaglandin D2; Prostaglandins D; Time Factors

Topics: Arachidonic Acid; Arachidonic Acids; Cyclooxygenase Inhibitors; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Leukotriene B4; Lipoxygenase Inhibitors; Lung; Mast Cells; Models, Biological; Prostaglandin D2; Prostaglandins D; Respiratory Tract Diseases; SRS-A

Arachidonic acid metabolism has been explored in preparations of purified human lung mast cells prelabeled with arachidonic acid (AA). Cells were of 83 to greater than 96% purity, and each experiment was performed with four to six different preparations of mast cells. After overnight culture of the purified cells in the presence of 3H-AA, followed by extensive washing in buffer, mast cell uptake of labeled AA was 61.4 +/- 14.8 pmol/10(6) cells with 21 +/- 2.4% of the label in phospholipids, 73 +/- 2.1% in neutral lipids, and 3.6 +/- 0.8% as free AA. Analysis of the distribution of radioactivity in phospholipid classes revealed 51.4 +/- 5.5% of the label in phosphatidylcholine, 14.5 +/- 1.6% in phosphatidylinositol, 12.0 +/- 3.0% in phosphatidylethanolamine, and 9.1 +/- 2.4% in sphingomyelin, with the rest in other phospholipid classes. Challenge of these cells with an optimal concentration of anti-IgE led to the release of 20 +/- 4.0% of cellular histamine and to a reduction in labeled phosphatidylcholine and phosphatidylinositol to 75.5 +/- 8.8% and 84.2 +/- 4.5% of the control levels, respectively, (p less than 0.05); anti-IgE challenge produced no statistically significant change in the quantities of other labeled phospholipids. Activation of human lung mast cells with anti-IgE led to the release of 3.4 +/- 1.3% of the cellular 3H as AA and AA metabolites (1.5 +/- 0.6% as unmetabolized AA) in conjunction with 16 +/- 4.3% of the cellular histamine. Although activation of human lung mast cells with ionophore A23187 caused 70 +/- 1.1% histamine release, a similar quantity of AA and AA metabolites was released (a total of 4.0 +/- 0.8% with 2.3 +/- 1.5% as unmetabolized AA). Analysis of the released metabolites by liquid scintillation spectrometry after high performance liquid chromatography separation showed that approximately equal amounts of metabolites were produced after mast cell activation with anti-IgE and ionophore A23187. In this series of experiments approximately equal amounts of cyclooxygenase and lipoxygenase products were generated.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Antibodies, Anti-Idiotypic; Arachidonic Acid; Arachidonic Acids; Histamine Release; Humans; Hydroxyeicosatetraenoic Acids; Immunoglobulin E; Indomethacin; Leukotriene B4; Lung; Mast Cells; Prostaglandin D2; Prostaglandins D; SRS-A

The capacity of chicken aorta to produce prostaglandins both from exogenous and endogenous arachidonic acid has been evaluated. The metabolism of arachidonic acid in this tissue is mainly directed to PGE2 and, in contrast to mammalian species, virtually no prostacyclin synthetase is present. However, the capacity of chicken thrombocytes to generate thromboxane A2 and 12-L-hydroxy-5, 8, 10, 14-eicosatetraenoic acid is similar to that observed for the mammalian blood platelets.

Topics: Animals; Aorta; Arachidonic Acid; Arachidonic Acids; Blood Platelets; Chickens; Dinoprost; Dinoprostone; Epoprostenol; Hydroxyeicosatetraenoic Acids; Male; Muscle, Smooth, Vascular; Prostaglandin D2; Prostaglandins; Prostaglandins D; Prostaglandins E; Prostaglandins F; Thromboxane A2; Turkeys