title: αB-crystallin reduces ristocetin‑induced soluble CD40 ligand release in human platelets: suppression of thromboxane A2 generation.
abstract: Our group has previously shown that αB-crystallin (HSPB5), a small heat shock protein, inhibits human platelet aggregation by ristocetin, an activator of glycoprotein Ib/IX/V. In addition, it was demonstrated that glycoprotein Ib/IX/V activation induces soluble CD40 (sCD40) ligand release via thromboxane (TX) A2. In the present study, the effect of αB-crystallin on the ristocetin-induced sCD40 ligand release in human platelets was investigated. The ristocetin-induced release of sCD40 ligand was suppressed by αB-crystallin. In addition, αB-crystallin reduced the ristocetin-stimulated production of 11-dehydro-TX B2, a stable metabolite of TXA2. αB-crystallin did not suppress the platelet aggregation induced by U46619, a TXA2 receptor agonist. αB-crystallin had little effect on the U46619-induced phosphorylation of p38 mitogen-activated protein kinase or sCD40 ligand release. In addition, αB-crystallin failed to reduce the binding of SZ2, a monoclonal antibody against the sulfated sequence in the α-chain of glycoprotein Ib, to the ristocetin-stimulated platelets. These results strongly suggest that αB-crystallin extracellularly suppresses ristocetin-stimulated release of sCD40 ligand by inhibiting the TXA2 production in human platelets.
authors.affiliation: Department of Neurosugery, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Tsujimoto
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Doi
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Kuroyanagi
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Iida
authors.affiliation: Department of Neurosugery, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Enomoto
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Iida
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ogura
authors.affiliation: Department of Orthopedic Surgery, Nagoya University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8603, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
authors.affiliation: Department of Neurosugery, Gifu University Graduate School of Medicine, Gifu, Gifu 501‑1194, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Iwama
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000633:toxicity; D000328:Adult; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D023201:CD40 Ligand / Q000032:analysis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D012310:Ristocetin / Q000633:toxicity*; D013928:Thromboxane A2 / Q000032:analysis / Q000378:metabolism*; D038203:alpha-Crystallin B Chain / Q000276:immunology / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D038203:alpha-Crystallin B Chain; D012310:Ristocetin; D023201:CD40 Ligand; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D048051:p38 Mitogen-Activated Protein Kinases