Integrin GPIIIa49-57 is the pivotal switch controlling platelet fragmentation
Integrin GPIIIa49-57 is the pivotal switch controlling platelet fragmentation
复制标题
整合素 GPIIIa49-57 是控制血小板碎片的关键开关
DOI：
10.3109/09537104.2015.1010440
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发表时间：
2015-03
期刊：
影响因子：
3.3
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
--
作者：
Wang, Jing;Hong, Tao;Dang, Suying;Zhang, Wei
在HIV-1免疫相关性血小板减少症(HIV-1-ITP)患者中检测到独特的抗血小板整合素GPIIIa49-66(CAPESIEFPVSEARVLED)的自体抗体，该抗体能通过释放活性氧(ROS)诱导补体非依赖性血小板碎裂。然而，不同的患者单抗或相似的兔多克隆单抗诱导血小板裂解的效率不同，其原因尚不清楚。本研究利用杂交瘤技术制备了一批针对GPIIa49-66区不同位点的鼠源性单抗。所有这些单抗都能与人血小板结合。其中，克隆1E7和5A10靶向GPIIIa49-57(CAPESIEFP，命名为P1)，克隆1C1和1E5靶向GPIIIA57-(PVSEARVL，命名P2)，克隆4D5和5F8靶向GPIIIa59-66(SEARVLED，命名P3)。用这些单抗与人血小板共同孵育，抗P1单抗诱导的血小板碎裂率是对照单抗的5-6倍(5A10是6倍，1E7是5.6倍)。而抗P2(1c1)和P3(5F8)单抗诱导的血小板碎裂率仅为对照单抗的1.9倍和1.1倍。因此，我们的数据表明，血小板整合素GPIIIa49-57是控制血小板断裂的关键开关。
Abstract Unique autologous antibodies (Abs) against platelet integrin GPIIIa49-66 (CAPESIEFPVSEARVLED) have been detected in patients with HIV-1 immune-related thrombocytopenia (HIV-1-ITP), which is capable of inducing complement-independent platelet fragmentation through reactive oxygen species (ROS) release. However, the efficiency of inducing platelet fragmentation is inconsistent among the different patient Abs or similar rabbit polyclonal Abs against the region and the reason remains unclear. In this study, we developed a batch of murine monoclonal antibodies (mAbs) against different locus of GPIIIa49-66 region by hybridoma technology. All these mAbs are capable of binding to human platelets. Among these mAbs, clones 1E7 and 5A10 were identified to target the epitope of GPIIIa49-57 (CAPESIEFP, named P1); clones 1C1 and 1E5 target GPIIIa57-64 (PVSEARVL, named P2), and clones 4D5 and 5F8 target GPIIIa59-66 (SEARVLED, named P3). By incubation of human platelets with these mAbs, the platelet fragmentation induced by mAbs against P1 was 5–6 folds higher than that by the control mAb (6-fold for 5A10 and 5.6-fold for 1E7). However, platelet fragmentation induced by mAbs against P2 (1C1) and P3 (5F8) was only 1.9- and 1.1-fold higher than that by the control mAb, respectively. Thus, our data demonstrate that platelet integrin GPIIIa49-57 is the pivotal switch controlling platelet fragmentation.
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DOI：
--
发表时间：
1956
期刊：
Progress in hematology
影响因子：
--
作者：
G. Arimura;Harrington Wj;Minnich
通讯作者：
G. Arimura;Harrington Wj;Minnich
影响因子：
15.9
作者：
Nardi, M;Feinmark, SJ;Karpatkin, S
通讯作者：
Karpatkin, S
DOI：
--
发表时间：
1982
期刊：
Sangre
影响因子：
--
作者：
J. Sánchez Fayos
通讯作者：
J. Sánchez Fayos
影响因子：
3.8
作者：
Zhang, Wei
通讯作者：
Zhang, Wei
DOI：
10.1073/pnas.94.14.7589
发表时间：
1997-07
影响因子：
11.1
作者：
M. Nardi;Lin-Xing Liu;Simon Karpatkin
通讯作者：
M. Nardi;Lin-Xing Liu;Simon Karpatkin