title: Effect of antithrombin III on glycoprotein Ib/IX/V activation in human platelets: suppression of thromboxane A2 generation.
abstract: We have previously shown that ristocetin, an activator of glycoprotein Ib/IX/V, induces release of soluble CD40 (sCD40) ligand via thromboxane (TX) A(2) production from human platelets. In the present study, we investigated the effect of antithrombin-III (AT-III), an anticoagulant, on the ristocetin-induced glycoprotein Ib/IX/V activation in human platelets. AT-III inhibited ristocetin-stimulated platelet aggregation. The ristocetin-induced production of 11-dehydro-TXB(2), a stable metabolite of TXA(2), and the release of sCD40 ligand were suppressed by AT-III. AT-III also reduced the ristocetin-stimulated secretion of platelet-derived growth factor (PDGF)-AB. AT-III failed to affect U46619-, a TXA(2) receptor agonist, induced levels of p38 mitogen-activated protein kinase phosphorylation or sCD40 ligand release. AT-III reduced the binding of SZ2, a monoclonal antibody to the sulfated sequence in the α-chain of glycoprotein Ib, to the ristocetin-stimulated platelets. These results strongly suggest that AT-III reduced ristocetin-stimulated release of sCD40 ligand due to inhibiting TXA(2) production in human platelets.
authors: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors: Tomoaki
authors: T
authors: Doi
authors: Haruhiko
authors: H
authors: Tokuda
authors: Rie
authors: R
authors: Matsushima-Nishiwaki
authors: Nguyen The
authors: NT
authors: Cuong
authors: Yasunari
authors: Y
authors: Kageyama
authors: Yuko
authors: Y
authors: Iida
authors: Akira
authors: A
authors: Kondo
authors: Shigeru
authors: S
authors: Akamatsu
authors: Takanobu
authors: T
authors: Otsuka
authors: Hiroki
authors: H
authors: Iida
authors: Osamu
authors: O
authors: Kozawa
authors: Shinji
authors: S
authors: Ogura
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000925:Anticoagulants / Q000494:pharmacology / Q000502:physiology*; D000990:Antithrombin III / Q000494:pharmacology / Q000502:physiology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019013:CD40 Antigens / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D015539:Platelet Activation; D010974:Platelet Aggregation; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D053657:Platelet-Rich Plasma / Q000166:cytology; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012310:Ristocetin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D019013:CD40 Antigens; D019038:Platelet Glycoprotein GPIb-IX Complex; D010982:Platelet-Derived Growth Factor; C095477:platelet-derived growth factor AB; D012310:Ristocetin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000990:Antithrombin III; D048051:p38 Mitogen-Activated Protein Kinases