GMP-140, A PLATELET ALPHA-GRANULE MEMBRANE-PROTEIN, IS ALSO SYNTHESIZED BY VASCULAR ENDOTHELIAL-CELLS AND IS LOCALIZED IN WEIBEL-PALADE BODIES

GMP-140, A PLATELET ALPHA-GRANULE MEMBRANE-PROTEIN, IS ALSO SYNTHESIZED BY VASCULAR ENDOTHELIAL-CELLS AND IS LOCALIZED IN WEIBEL-PALADE BODIES
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DOI:
10.1172/jci114175
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发表时间:
1989-07-01
影响因子:
15.9
通讯作者:
BAINTON, DF
BAINTON, DF
中科院分区:
医学1区
文献类型:
--
作者:
MCEVER, RP;BECKSTEAD, JH;BAINTON, DF

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我们使用免疫过氧化物酶程序来检查血小板α-颗粒膜蛋白GMP-140的组织分布。除了巨核细胞和血小板中存在 GMP-140 抗原外,在多种人体器官的血管内皮细胞中也发现了 GMP-140 抗原,但在其他类型的分泌细胞中未检测到。 [35S]半胱氨酸标记的人脐静脉内皮细胞合成了含有复杂的N-连接寡糖的GMP-140分子,类似于先前在血小板和巨核细胞HEL细胞系中所证明的分子。对内皮细胞的冷冻薄片使用免疫金程序,我们发现 GMP-140 抗原定位于电子致密存储颗粒的膜上。在双标记实验中,GMP-140 与 vWf 共定位,表明这些颗粒是 Weibel-Palade 小体。当内皮细胞受到组胺刺激时,GMP-140 迅速重新分布到质膜上。细胞裂解物的免疫测定表明,相对于总细胞蛋白,人脐静脉内皮细胞中存在的 GMP-140 少于血小板中的 GMP-140。血小板和内皮细胞的分泌颗粒中 GMP-140 的有限表达表明它在血管系统中具有特定的功能,而不是与诱导分泌相关的一般作用。
We used an immunoperoxidase procedure to examine the tissue distribution of the platelet .alpha.-granule membrane protein, GMP-140. In addition to its presence in megakaryocytes and platelets, GMP-140 antigen was found in vascular endothelial cells of diverse human organs, but it was not detected in other types of secretory cells. [35S]Cysteine-labeled human umbilical vein endothelial cells synthesized a GMP-140 molecule containing complex N-linked oligosaccharides similar to those previously demonstrated in platelets and the megakaryocytic HEL cell line. Using an immunogold procedure on frozen thin sections of endothelial cells, we found GMP-140 antigen to be localized to membranes of electron-dense storage granules. In double-label experiments there was colocalization of GMP-140 with vWf, indicating that these granules are Weibel-Palade bodies. When endothelial cells were stimulated with histamine, GMP-140 rapidly redistribution to the plasma membrane. Immunoassays of cell lysates indicated that, relative to total cell protein, less GMP-140 is present in human umbilical vein endothelial cells than in platelets. The restricted expression of GMP-140 in secretory granules of platelets and endothelium suggests that it has a specific function in the vascular system rather than a general role related to inducible secretion.