Ligand bridging mediates integrin alpha IIb beta 3 (platelet GPIIB-IIIA) dependent homotypic and heterotypic cell-cell interactions.

Ligand bridging mediates integrin alpha IIb beta 3 (platelet GPIIB-IIIA) dependent homotypic and heterotypic cell-cell interactions.
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配体桥接介导整合素 α IIb beta 3(血小板 GPIIB-IIIA)依赖性同型和异型细胞间相互作用。

DOI:
10.1172/jci115412
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发表时间:
1991
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Ginsberg,MH
Ginsberg,MH
中科院分区:
--
文献类型:
--
作者:
Gawaz,MP;Loftus,JC;Bajt,ML;Frojmovic,MM;Plow,EF;Ginsberg,MH

文献摘要

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通过双色流式细胞术分析了携带重组整合素α IIb β 3(血小板GPIIb-IIIa)的细胞的聚集。与正常血小板一样,聚集需要功能性α IIb β 3、α IIb β 3的“活化”以及纤维蛋白原(fg)与α IIb β 3的结合。细胞聚集需要两个相互作用的细胞表达功能性α IIb β 3,因为结合缺陷突变体α IIb β 3(D119-Y)不能支持与携带野生型α IIb β 3的细胞的相互作用。此外,携带静息α IIb β 3的细胞被整合到由携带组成型活性突变体α IIb β 3(β 1-2)的细胞形成的聚集体中,表明相互作用对中只有一个细胞必须被激活。最后,异型相互作用发生在携带活化的α IIb β 3的细胞和携带α V β 3的细胞之间,α V β 3是一种存在于内皮细胞和肿瘤细胞上的结合FG的整合素。因此,在fg结合整联蛋白之间的配体桥接代表细胞-细胞相互作用的机制,携带静息α IIb β 3的细胞(例如,静息血小板)可以被整合到由携带活化的α IIb β 3的细胞形成的聚集体中,而α IIb β 3介导与携带其他fg受体的细胞的异型相互作用。图片
The aggregation of cells bearing recombinant integrin alpha IIb beta 3 (platelet GPIIb-IIIa) has been analyzed by two-color flow cytometry. As in normal platelets, aggregation requires functional alpha IIb beta 3, "activation" of alpha IIb beta 3, and fibrinogen (fg) binding to alpha IIb beta 3. Cellular aggregation required that both interacting cells express functional alpha IIb beta 3, because a binding defective mutant, alpha IIb beta 3 (D119----Y), failed to support interaction with wild type alpha IIb beta 3-bearing cells. In addition, cells bearing resting alpha IIb beta 3 were incorporated into aggregates formed by cells bearing a constitutively active mutant, alpha IIb beta 3 (beta 1-2), indicating that only one of the cells in an interacting pair must be activated. Finally, heterotypic interactions occurred between cells bearing activated alpha IIb beta 3 and cells bearing alpha V beta 3, a fg-binding integrin present on endothelial and tumor cells. Thus, ligand bridging between fg-binding integrins represents a mechanism of cell-cell interaction, cells bearing resting alpha IIb beta 3 (e.g., resting platelets) may be incorporated into aggregates formed by cells bearing activated alpha IIb beta 3, and alpha IIb beta 3 mediates heterotypic interactions with cells bearing other fg receptors.Images