GPIIb-IIIa antagonists cause rapid disaggregation of platelets pre-treated with cytochalasin D. Evidence that the stability of platelet aggregates depends on normal cytoskeletal assembly
GPIIb-IIIa antagonists cause rapid disaggregation of platelets pre-treated with cytochalasin D. Evidence that the stability of platelet aggregates depends on normal cytoskeletal assembly
复制标题
DOI：
10.1080/09537109876744
复制
发表时间：
1998-01-01
期刊：
影响因子：
3.3
通讯作者：
Heptinstall, S
中科院分区：
文献类型：
--
作者：
May, JA;Ratan, H;Heptinstall, S
血小板活化伴随着血小板细胞骨架组成的变化，某些蛋白质快速掺入和置换。在这里，我们通过用细胞松弛素D（CyD）预处理血小板来抑制细胞骨架组装，并研究了对所形成的聚集体的稳定性的影响。实验在柠檬酸化和水蛭素化的富血小板血浆（PRP）中进行，并由腺苷二磷酸（ADP）、胶原、TXA（2）模拟物U46619和肾上腺素诱导聚集。在加入EDTA或GpIIb-IIIa拮抗剂如MK-852和GR 144053 F后，形成的聚集体中的血小板迅速解聚，所有这些都是干扰纤维蛋白原与GpIIb-IIIa相互作用能力的试剂。无论使用何种凝集剂，在柠檬酸化和水蛭素化PRP中均发生这种情况。相反，其他一些药物（伊洛前列素和ARL 66096）引起的解聚率似乎不受CyD影响。还获得了CyD对ADP引起的细胞骨架变化的影响以及后续添加MK-852对细胞骨架的影响的信息，结果表明，CyD延缓了某些蛋白质（肌动蛋白、肌球蛋白、α-辅肌动蛋白、肌动蛋白结合蛋白和66 K蛋白）掺入细胞骨架，随后加入MK-852导致其中一些蛋白质快速置换，并重新掺入31 K蛋白质。结果表明，血小板活化后细胞骨架的早期变化有助于形成的聚集体的稳定性，并且这些早期变化的干扰导致聚集体容易被干扰GpIIb-IIIa-纤维蛋白原复合物形成的试剂分解。
Platelet activation is accompanied by changes in the composition of the platelet cytoskeleton with rapid incorporation and displacement of certain proteins. Here we have inhibited cytoskeletal assembly by pretreating platelets with cytochalasin D (CyD) and investigated the effect on the stability of the aggregates that form, The experiments were performed in both citrated and hirudinized platelet-rich plasma (PRP) and aggregation was induced by adenosine diphosphate (ADP), collagen, the TXA(2)-mimetic U46619 and adrenaline. Platelets in the aggregates that formed, underwent rapid disaggregation on addition of EDTA or a GpIIb-IIIa antagonist such as MK-852 and GR144053F, all of which are agents that interfere with the ability of fibrinogen to interact with GpIIb-IIIa. This was the case irrespective of the aggregating agent used and occurred in both citrated and hirudinized PRP, In contrast, the rate of disaggregation brought about by some other agents, iloprost and ARL 66096, appeared to be unaffected by CyD, Information was also obtained on the effects of CyD on the cytoskeletal changes brought about by ADP and the effects on the cytoskeleton of subsequent addition of MK-852, The results show that CyD retards the incorporation of certain proteins (actin, myosin, alpha-actinin, actin binding protein and a 66 K protein) into the cytoskeleton and that subsequent addition of MK-852 results in rapid displacement of some of these with re-incorporation of a 31 K protein. The results suggest that the early changes in the cytoskeleton following platelet activation contribute to the stability of the aggregates that form, and that interference with these early changes results in aggregates that are easily disassembled by agents that interfere with GpIIb-IIIa-fibrinogen complex formation.