A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa.

A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa.
复制标题

完全阻断纤维蛋白原与血小板结合的鼠单克隆抗体在正常血小板中产生血栓样无力状态,并与糖蛋白 IIb 和/或 IIIa 结合。

DOI:
--
复制
发表时间:
1983
影响因子:
15.9
通讯作者:
C. Sullivan
C. Sullivan
中科院分区:
医学1区
文献类型:
--
作者:
B. Coller;E. Peerschke;L. Scudder;C. Sullivan

文献摘要

参考文献

被引文献

相似文献

为了更好地定义纤维蛋白原受体在血小板生理学中的作用并对其进行生物化学表征,通过杂交瘤技术借助功能筛选试验产生了完全阻断纤维蛋白原与血小板表面结合的鼠单克隆抗体。纯化的F(ab ')2片段和/或完整抗体完全阻断ADP、凝血酶或肾上腺素诱导的聚集以及ADP诱导的放射性标记的纤维蛋白原与血小板的结合。该抗体不阻断由瑞斯托卡林或ADP或凝血酶诱导的形状变化引起的甲醛固定的血小板的凝集。ADP和肾上腺素诱导的ATP释放被抗体完全抑制,但胶原蛋白和凝血酶诱导的释放的抑制是剂量依赖性的和部分的。该抗体还显着抑制血小板滞留在玻璃珠柱,血小板粘附到玻璃,凝块收缩。因此,该抗体诱导血栓形成样状态。免疫荧光研究证实了抗体对正常血小板和巨核细胞的特异性,并表明在血栓性血小板中可检测到的抗原明显减少。放射性标记的抗体与正常血小板上平均约40,000个位点结合,但与血小板无力症患者血小板上不到2,000个位点结合。抗体免疫沉淀糖蛋白IIb和IIIa,并且两种糖蛋白结合到抗体的亲和柱。这些研究表明,可能存在一个对所有纤维蛋白原分子的结合至关重要的单一解剖学位点,并且该位点最有可能位于糖蛋白IIb/IIIa复合物上。它还表明,凝血酶原的表型可以完全占的基础上抑制纤维蛋白原结合血小板。
To define better the role of the fibrinogen receptor in platelet physiology and to characterize it biochemically, a murine monoclonal antibody that completely blocks the binding of fibrinogen to the platelet surface was produced by the hybridoma technique with the aid of a functional screening assay. Purified F(ab')2 fragments and/or intact antibody completely blocked aggregation induced by ADP, thrombin, or epinephrine and the binding of radiolabeled fibrinogen to platelets induced by ADP. The antibody did not block agglutination of formaldehyde-fixed platelets by ristocetin or shape change induced by either ADP or thrombin. ADP- and epinephrine-induced release of ATP was completely inhibited by the antibody, but inhibition of release induced by collagen and thrombin was dose dependent and partial. The antibody also dramatically inhibited platelet retention in glass-bead columns, platelet adhesion to glass, and clot retraction. Thus, the antibody induced a thrombasthenic-like state. Immunofluorescent studies confirmed the specificity of the antibody for normal platelets and megakaryocytes and suggested that there is a marked decrease in detectable antigen in thrombasthenic platelets. Radiolabeled antibody bound to an average of approximately 40,000 sites on normal platelets but it bound to less than 2,000 sites on the platelets of a patient with thrombasthenia. The antibody immunoprecipitated both glycoproteins IIb and IIIa, and both glycoproteins bound to an affinity column of the antibody. These studies indicate that there is probably a single anatomic site that is crucial to the binding of all fibrinogen molecules and that this site is most likely on the glycoprotein IIb/IIIa complex. It also suggests that the thrombasthenic phenotype can be completely accounted for on the basis of the inhibition of fibrinogen binding to platelets.
血小板膜糖蛋白 IIb 和 IIIa 的分离、纯化和部分表征。
DOI: --
发表时间: 1981
期刊: The Journal of biological chemistry
影响因子: --
作者:
Leung,LL;Kinoshita,T;Nachman,RL
通讯作者: Nachman,RL
胰凝乳蛋白酶和二磷酸腺苷对正常人和血小板无力症血小板上纤维蛋白原受体暴露的影响。
DOI: --
发表时间: 1981
期刊: The Journal of biological chemistry
影响因子: --
作者:
Kornecki,E;Niewiarowski,S;Morinelli,TA;Kloczewiak,M
通讯作者: Kloczewiak,M
DOI: 10.1182/blood.v61.1.140.140
发表时间: 1983
期刊: Blood
影响因子: 20.3
作者:
G. Minno;P. Thiagarajan;B. Perussia;J. Martínez;S. Shapiro;G. Trinchieri;S. Murphy
通讯作者: G. Minno;P. Thiagarajan;B. Perussia;J. Martínez;S. Shapiro;G. Trinchieri;S. Murphy
DOI: --
发表时间: 1982
期刊: The Journal of biological chemistry
影响因子: --
作者:
Howard,L;Shulman,S;Sadanandan,S;Karpatkin,S
通讯作者: Karpatkin,S
DOI: 10.1172/jci109983
发表时间: 1980-12
期刊: The Journal of clinical investigation
影响因子: --
作者:
R. McEver;N. Baenziger;P. Majerus
通讯作者: R. McEver;N. Baenziger;P. Majerus