ＪＣＩ：能抑制血栓形成的抗体
日本研究人员4月1日在美国《临床检查杂志》（The Journal of Clinical Investigation）上发表文章称，他们找到一种使血液较难凝固的抗体，它可以抑制血栓形成。
血管组织中所含胶原蛋白纤维缠绕在血液中的血小板上，会导致血栓形成。日本滋贺县立大学和京都大学的研究人员发现，患有血液难以凝固疾病的病人，其血液中含有一种防止血小板和胶原蛋白结合的抗体。研究人员人工合成了这种抗体，并对实验鼠进行了血栓形成对比研究。结果，普通实验鼠在特定条件下形成了血栓，而事先注射了这种人工合成抗体的实验鼠，在同样条件下则没有形成血栓。
血栓可引起脑梗塞和心肌梗塞等。阿司匹林、肝素等抗凝血药物需要增减药量以调节疗效，一旦药量过度，容易引发脑出血等内出血。研究人员说，人工合成的抗体即使加大用量也不会导致内出血，以此为基础有望在10年内开发出抗血栓新药。（来源：新华网 钱铮）
生物谷推荐原始出处：
（The Journal of Clinical Investigation），doi：doi:10.1172/JCI32513，Hiroshi Takayama，Shoji Furusako
A novel antiplatelet antibody therapy that induces cAMP-dependent endocytosis of the GPVI/Fc receptor γ-chain complex
1Department of Health and Nutrition, School of Human Cultures, The University of Shiga Prefecture, Shiga, Japan.
2Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
3Pharmaceutical Research Center, Mochida Pharmaceutical Co. Ltd., Shizuoka, Japan.
Platelet adhesion to vascular subendothelium, mediated in part by interactions between collagen and glycoprotein VI (GPVI) complexed with Fc receptor γ-chain, is crucial for thrombus formation. Antiplatelet therapy benefits patients with various thrombotic and ischemic diseases, but the safety and efficacy of existing treatments are limited. Recent data suggest GPVI as a promising target for a novel antiplatelet therapy, for example, GPVI-specific Abs that deplete GPVI from the surface of platelets. Here, we characterized GPVI-specific auto-Abs (YA-Abs) from the first reported patient with ongoing platelet GPVI deficiency caused by the YA-Abs. To obtain experimentally useful human GPVI–specific mAbs with characteristics similar to YA-Abs, we generated human GPVI–specific mouse mAbs and selected 2 representative mAbs, mF1201 and mF1232, whose binding to GPVI was inhibited by YA-Abs. In vitro, mF1201, but not mF1232, induced human platelet activation and GPVI shedding, and mF1232 inhibited collagen-induced human platelet aggregation. Administration of mF1201 and mF1232 to monkeys caused GPVI immunodepletion with and without both significant thrombocytopenia and GPVI shedding, respectively. When a human/mouse chimeric form of mF1232 (cF1232) was labeled with a fluorescent endocytosis probe and administered to monkeys, fluorescence increased in circulating platelets and surface GPVI was lost. Loss of platelet surface GPVI mediated by cF1232 was successfully reproduced in vitro in the presence of a cAMP-elevating agent. Thus, we have characterized cAMP-dependent endocytosis of GPVI mediated by a human GPVI–specific mAb as what we believe to be a novel antiplatelet therapy.
- 众说风云 (已有0条评论)
