Biomaterial Database

Synergistic effect of thromboxane A2 and N-formylmethionylleucylphenylalanine on platelet-activating factor synthesis in human polymorphonuclear neutrophils. 1991

J Kishino, and K Hanasaki, and T Kato, and H Arita

Shionogi Research Laboratories, Shionogi & Co., Osaka Japan.

The effects of thromboxane A2 (TXA2) on the synthesis of platelet-activating factor (PAF) and leukotriene B4 (LTB4) were studied using human polymorphonuclear neutrophils (PMN). Scatchard analysis for binding experiments using [3H]S-145, a specific TXA2/prostaglandin H2 (PGH2) receptor antagonist, revealed the existence of a single class of binding sites (Kd = 83.0 +/- 2.8 nM, Bmax = 113.0 +/- 3.1 fmol/2.10(6) cells) in human PMN. Upon stimulation with a combination of U46619, a TXA2 mimetic agonist, and N-formylmethionylleucylphenylalanine (FMLP, 1 microM), the synthesis of PAF was detected, although this was not significantly enhanced by U46619 or FMLP alone. The maximal production of PAF as well as the maximal activity of acetyl-CoA acetyltransferase was observed at approx. 20 min after addition of both stimuli. The effects of U46619 plus FMLP on PAF synthesis showed dose dependence to different concentrations of U46619 (0.1-10 microM), and were completely inhibited by S-145. Contrarily, no significant amounts of LTB4 were detected by radioimmunoassay during the stimulation with U46619 and FMLP. These results suggest that TXA2 and FMLP synergistically activate human PMN to induce PAF synthesis and this effect of TXA2 is mediated through its specific receptor.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D007975	Leukotriene B4	The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990)	5,12-HETE,5,12-diHETE,LTB4,Leukotriene B,Leukotriene B-4,Leukotrienes B,5,12 HETE,5,12 diHETE,B-4, Leukotriene,Leukotriene B 4
D009240	N-Formylmethionine Leucyl-Phenylalanine	A formylated tripeptide originally isolated from bacterial filtrates that is positively chemotactic to polymorphonuclear leucocytes, and causes them to release lysosomal enzymes and become metabolically activated.	F-Met-Leu-Phe,N-Formyl-Methionyl-Leucyl-Phenylalanine,Formylmet-Leu-Phe,Formylmethionyl Peptide,Formylmethionyl-Leucyl-Phenylalanine,Formylmethionylleucylphenylalanine,N-Formylated Peptide,N-formylmethionyl-leucyl-phenylalanine,fMet-Leu-Phe,F Met Leu Phe,Formylmet Leu Phe,Formylmethionyl Leucyl Phenylalanine,Leucyl-Phenylalanine, N-Formylmethionine,N Formyl Methionyl Leucyl Phenylalanine,N Formylated Peptide,N Formylmethionine Leucyl Phenylalanine,N formylmethionyl leucyl phenylalanine,Peptide, Formylmethionyl,Peptide, N-Formylated,fMet Leu Phe
D009504	Neutrophils	Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.	LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D010972	Platelet Activating Factor	A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.	AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D011450	Prostaglandin Endoperoxides, Synthetic	Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds.	Prostaglandin Endoperoxide Analogs,Prostaglandin Endoperoxide Analogues,Synthetic Prostaglandin Endoperoxides,Analogues, Prostaglandin Endoperoxide,Endoperoxide Analogues, Prostaglandin,Endoperoxides, Synthetic Prostaglandin
D011982	Receptors, Prostaglandin	Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).	Prostaglandin Receptors,Prostaglandin Receptor,Receptor, Prostaglandin,Receptors, Prostaglandins,Prostaglandins Receptors
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005229	Fatty Acids, Monounsaturated	Fatty acids which are unsaturated in only one position.	Monounsaturated Fatty Acid,Acid, Monounsaturated Fatty,Acids, Monounsaturated Fatty,Fatty Acid, Monounsaturated,Monounsaturated Fatty Acids
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man