Konkle B A, Shapiro S S, Asch A S, Nachman R L
Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
J Biol Chem. 1990 Nov 15;265(32):19833-8.
Platelet glycoprotein Ib is a major platelet membrane protein composed of two disulfide-linked chains, termed the alpha and beta chains. The larger alpha chain (GpIb alpha), a platelet receptor for von Willebrand factor, plays a major role in mediating platelet adhesion to the subendothelium. Our laboratories have previously reported synthesis of a protein in human endothelial cells that is immunoprecipitated with polyclonal and monoclonal antibodies to platelet GpIb alpha. Lopez et al. (Lopez, J. A., Chung, D. W., Fujikawa, K., Hagan, F. S., Papayannopoulou, T., and Roth, G. J. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 5615-5619) have reported the cloning of GpIb alpha from a human erythroleukemia (HEL) cell cDNA library. Using this clone as probe, we have isolated two partial GpIb alpha clones from a human umbilical vein endothelial cell lambda gt11 cDNA library. These clones were localized within HEL-derived GpIb alpha cDNA by sequence and restriction enzyme analysis. Additionally, they detected the same message species in HEL and tonsilar RNA that was detected with the HEL GpIb alpha cDNA. Low level GpIb alpha mRNA expression was detected in cultured human umbilical vein endothelial cells, which was increased by treatment of the cells with tumor necrosis factor-alpha. This effect was enhanced by pretreatment with interferon-gamma. Additionally, localization of GpIb alpha in endothelium of fresh tonsilar tissue was demonstrated by immunohistochemistry and in situ hybridization. GpIb alpha may play a role in mediating platelet or other effector cell adhesion to activated endothelium.
血小板糖蛋白Ib是一种主要的血小板膜蛋白，由两条通过二硫键连接的链组成，分别称为α链和β链。较大的α链（GpIbα）是血管性血友病因子的血小板受体，在介导血小板与内皮下层的黏附中起主要作用。我们实验室之前报道过，在人内皮细胞中合成了一种蛋白质，该蛋白质可被针对血小板GpIbα的多克隆和单克隆抗体免疫沉淀。洛佩兹等人（洛佩兹，J.A.，钟，D.W.，藤川，K.，哈根，F.S.，帕帕扬诺普洛，T.，和罗斯，G.J.（1987年）《美国国家科学院院刊》84，5615 - 5619）报道了从人红白血病（HEL）细胞cDNA文库中克隆GpIbα。以该克隆为探针，我们从人脐静脉内皮细胞λgt11 cDNA文库中分离出了两个部分GpIbα克隆。通过序列和限制酶分析，这些克隆被定位在源自HEL的GpIbα cDNA内。此外，它们在HEL和扁桃体RNA中检测到了与HEL GpIbα cDNA检测到的相同的信使RNA种类。在培养的人脐静脉内皮细胞中检测到低水平的GpIbα mRNA表达，用肿瘤坏死因子-α处理细胞可使其增加。用干扰素-γ预处理可增强这种效应。此外，通过免疫组织化学和原位杂交证明了GpIbα在新鲜扁桃体组织内皮中的定位。GpIbα可能在介导血小板或其他效应细胞与活化内皮的黏附中起作用。
