Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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"Köpfe" der aktuellen Meldungen:

Nina Höller

Nariae Baik-Schneditz

Bernhard Schwaberger

Lukas Peter Mileder

Niels Hammer

Gerhard Pichler

Roland Malli

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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Böhm, E; Sturm, GJ; Weiglhofer, I; Sandig, H; Shichijo, M; McNamee, A; Pease, JE; Kollroser, M; Peskar, BA; Heinemann, A.
11-Dehydro-thromboxane B2, a stable thromboxane metabolite, is a full agonist of chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) in human eosinophils and basophils.
J BIOL CHEM. 2004; 279: 7663-7670. Doi: 10.1074/jbc.M310270200 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz: Böhm Eva; Heinemann Akos
Co-Autor*innen der Med Uni Graz: Kollroser Manfred; Peskar Bernhard; Sturm Gunter
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Abstract:: Thromboxane (TX) A(2), a cyclooxygenase-derived mediator involved in allergic responses, is rapidly converted in vivo to a stable metabolite, 11-dehydro-TXB(2), which is considered to be biologically inactive. In this study, we found that 11-dehydro-TXB(2), but not the TXA(2) analogue U46,619 or TXB(2), activated eosinophils and basophils, as assayed by flow cytometric shape change. 11-Dehydro-TXB(2) was also chemotactic for eosinophils but did not induce, nor inhibit, platelet aggregation. Chemoattractant receptor-homologous molecule expressed on TH2 cells (CRTH2) is an important chemoattractant receptor expressed by eosinophils, basophils, and TH2 lymphocytes, and prostaglandin (PG)D(2) has been shown to be its principal ligand. 11-Dehydro-TXB(2) induced calcium flux mainly from intracellular stores in eosinophils, and this response was desensitized after stimulation with PGD(2) but not other eosinophil chemoattractants. Shape change responses of eosinophils and basophils to 11-dehydro-TXB(2) were inhibited by the thromboxane (TP)/CRTH2 receptor antagonist ramatroban, but not the selective TP antagonist SQ29,548, and were insensitive to pertussis toxin. The phospholipase C inhibitor U73,122 attenuated both 11-dehydro-TXB(2)- and PGD(2)-induced shape change. 11-Dehydro-TXB(2) also induced the chemotaxis of BaF/3 cells transfected with hCRTH2 but not naive BaF/3 cells. At a threshold concentration, 11-dehydro-TXB(2) had no antagonistic effect on CRTH2-mediated responses as induced by PGD2. These data show that 11-dehydro-TXB(2) is a full agonist of the CRTH2 receptor and hence might cause CRTH2 activation in cellular contexts where PGD-synthase is not present. Given its production in the allergic lung, antagonism of the 11-dehydro-TXB(2)/CRTH2axis may be of therapeutic relevance.
Find related publications in this database (using NLM MeSH Indexing): 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; Basophils - cytology; Calcium - metabolism; Carbazoles - pharmacology; Cell Size - drug effects; Chemotaxis, Leukocyte - drug effects; Comparative Study - drug effects; Enzyme Inhibitors - pharmacology; Eosinophils - cytology; Flow Cytometry - cytology; Humans - cytology; Hydrazines - pharmacology; Pertussis Toxin - pharmacology; Phospholipase C - antagonists and inhibitors; Prostaglandin D2 - pharmacology; Receptors, Immunologic - antagonists and inhibitors; Receptors, Prostaglandin - antagonists and inhibitors; Research Support, Non-U.S. Gov't - antagonists and inhibitors; Sulfonamides - pharmacology; Thromboxane B2 - analogs and derivatives; Transfection - analogs and derivatives