George J N, Pickett E B, Saucerman S, McEver R P, Kunicki T J, Kieffer N, Newman P J
J Clin Invest. 1986 Aug;78(2):340-8. doi: 10.1172/JCI112582.
The accurate definition of surface glycoprotein abnormalities in circulating platelets may provide better understanding of bleeding and thrombotic disorders. Platelet surface glycoproteins were measured on intact platelets in whole blood and platelet membrane microparticles were assayed in cell-free plasma using 125I-monoclonal antibodies. The glycoproteins (GP) studied were: GP Ib and GP IIb-IIIa, two of the major intrinsic plasma membrane glycoproteins; GMP-140, an alpha-granule membrane glycoprotein that becomes exposed on the platelet surface following secretion; and thrombospondin (TSP), an alpha-granule secreted glycoprotein that rebinds to the platelet surface. Thrombin-induced secretion in normal platelets caused the appearance of GMP-140 and TSP on the platelet surface, increased exposure of GP IIb-IIIa, and decreased antibody binding to GP Ib. Patients with adult respiratory distress syndrome had an increased concentration of GMP-140 and TSP on the surface of their platelets, demonstrating in vivo platelet secretion, but had no increase of platelet microparticles in their plasma. In contrast, patients after cardiac surgery with cardiopulmonary bypass demonstrated changes consistent with membrane fragmentation without secretion: a decreased platelet surface concentration of GP Ib and GP IIb with no increase of GMP-140 and TSP, and an increased plasma concentration of platelet membrane microparticles. These methods will help to define acquired abnormalities of platelet surface glycoproteins.
循环血小板表面糖蛋白异常的准确定义可能有助于更好地理解出血和血栓形成性疾病。使用¹²⁵I-单克隆抗体在全血中的完整血小板上测量血小板表面糖蛋白,并在无细胞血浆中检测血小板膜微粒。所研究的糖蛋白(GP)包括:主要的内在质膜糖蛋白中的两种,即GP Ib和GP IIb-IIIa;GMP-140,一种α-颗粒膜糖蛋白,在分泌后暴露于血小板表面;以及血小板反应蛋白(TSP),一种α-颗粒分泌的糖蛋白,可重新结合到血小板表面。正常血小板中凝血酶诱导的分泌导致血小板表面出现GMP-140和TSP,GP IIb-IIIa的暴露增加,以及抗体与GP Ib的结合减少。成人呼吸窘迫综合征患者血小板表面的GMP-140和TSP浓度增加,表明体内血小板有分泌,但血浆中血小板微粒没有增加。相比之下,接受体外循环心脏手术的患者表现出与无分泌的膜碎片形成一致的变化:血小板表面GP Ib和GP IIb浓度降低,GMP-140和TSP没有增加,并且血浆中血小板膜微粒浓度增加。这些方法将有助于确定血小板表面糖蛋白的获得性异常。