Lawler J, Cohen A M, Chao F C, Moriarty D J
Blood. 1986 Feb;67(2):555-8.
Essential thrombocythemia is a myeloproliferative disorder characterized by frequent bleeding and thrombotic complications. On a molecular level, two abnormalities of platelet thrombospondin have been identified: abnormal glycosylation of the intact 185,000-dalton chain has been detected and a shortened form of the thrombospondin chain is present. We have used two monoclonal antibodies and Lens culinaris lectin to probe the structure of thrombospondin in the platelets from three patients with essential thrombocythemia; one patient with polycythemia vera and two patients with secondary thrombocytosis. The presence of abnormal thrombospondin fragments with molecular weights of 160,000 and 30,000 was detected in the intact platelets and in the supernatant from thrombin-treated platelets, in all of the individuals except one of the secondary thrombocytosis patients. Monoclonal antibody binding studies indicate that both fragments are produced by proteolysis at a single site, which results in the removal of a 30,000-dalton fragment from the NH2-terminal. Lens culinaris lectin-binding studies revealed that some of the carbohydrate moieties of thrombospondin are near this cleavage site. The results are consistent with the hypothesis that the abnormal thrombospondin fragments observed under conditions of increased platelet production are due to increased susceptibility to proteolysis which, in turn, may be due to defective glycosylation.
原发性血小板增多症是一种骨髓增殖性疾病，其特征为频繁出血和血栓形成并发症。在分子水平上，已发现血小板凝血酶敏感蛋白存在两种异常：完整的185,000道尔顿链存在异常糖基化，并且存在凝血酶敏感蛋白链的缩短形式。我们使用两种单克隆抗体和菜豆凝集素，对三名原发性血小板增多症患者、一名真性红细胞增多症患者和两名继发性血小板增多症患者的血小板中凝血酶敏感蛋白的结构进行了探测。在除一名继发性血小板增多症患者外的所有个体的完整血小板和凝血酶处理血小板的上清液中，均检测到分子量为160,000和30,000的异常凝血酶敏感蛋白片段。单克隆抗体结合研究表明，这两种片段均由在单个位点的蛋白水解产生，这导致从NH2末端去除了一个30,000道尔顿的片段。菜豆凝集素结合研究显示，凝血酶敏感蛋白的一些碳水化合物部分靠近该切割位点。这些结果与以下假设一致：在血小板生成增加的情况下观察到的异常凝血酶敏感蛋白片段是由于蛋白水解敏感性增加所致，而蛋白水解敏感性增加反过来可能是由于糖基化缺陷。
