Hemostatic effects of phospholipid vesicles carrying fibrinogen gamma chain dodecapeptide in vitro and in vivo.
Hemostatic effects of phospholipid vesicles carrying fibrinogen gamma chain dodecapeptide in vitro and in vivo.
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DOI：
10.1021/bc050178g
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发表时间：
2005-11
影响因子：
4.7
通讯作者：
Y. Okamura;Ippei Maekawa;Y. Teramura;H. Maruyama;M. Handa;Y. Ikeda;S. Takeoka
中科院分区：
文献类型：
--
作者：
Y. Okamura;Ippei Maekawa;Y. Teramura;H. Maruyama;M. Handa;Y. Ikeda;S. Takeoka
我们研究了血小板替代品的原型，其表面上具有十二肽HHLGGAKQAGDV（H12）。该肽是纤维蛋白原γ链羧基末端序列（γ 400 -411），并特异性识别活化血小板表面上糖蛋白（GP）IIb/IIIa的活性形式。我们将H12与平均直径为220 nm的磷脂囊泡表面上的聚（乙二醇）链的末端缀合以制备H12-PEG-囊泡。H12-PEG-囊泡的半衰期通过PEG修饰显著延长，并且即使表面用PEG链修饰，囊泡表面上的H12识别GPIIb/IIIa的能力仍得以保持。H12-PEG-血管促进血小板体外血栓形成，血小板粘附在胶原固定的板，当血小板减少症模拟血液通过该板。基于PAC-1结合和P-选择素表达的流式细胞术分析，显示H12-PEG-囊泡不引起血小板活化。此外，H12-PEG-囊泡剂量依赖性地缩短血小板减少大鼠的尾部出血时间。已证实H12-PEG-囊泡具有止血作用，并且可能是输注到血小板减少患者中的人血小板浓缩物的替代物的合适候选物。
We studied prototypes of platelet substitutes that bear on their surface a dodecapeptide, HHLGGAKQAGDV (H12). The peptide is a fibrinogen gamma chain carboxy-terminal sequence (gamma400-411) and recognizes specifically the active form of glycoprotein (GP) IIb/IIIa on the surface of activated platelets. We conjugated H12 to the end of poly(ethylene glycol) chains on the surface of a phospholipid vesicle with an average diameter of 220 nm to prepare H12-PEG-vesicles. The half-life of the H12-PEG-vesicles was significantly prolonged by PEG modification, and the ability of H12 on the surface of the vesicle to recognize GPIIb/IIIa was maintained even though the surface was modified with PEG chains. The H12-PEG-veiscles enhanced the in vitro thrombus formation of platelets that were adhering to a collagen-immobilized plate, when thrombocytopenia-imitation blood was passed over the plate. Based on the flow cytometric analyses of PAC-1 binding and P-selectin expression, the H12-PEG-vesicles were shown not to cause platelet activation. Furthermore, the H12-PEG-vesicles dose-dependently shortened the tail bleeding time of thrombocytopenic rats. It was confirmed that the H12-PEG-vesicles had a hemostatic effect and may be a suitable candidate for an alternative to human platelet concentrates transfused into thrombocytopenic patients.