Naitoh Katsuki, Hosaka Yoshitaka, Honda Motoyasu, Ogawa Kumiko, Shirakawa Kamon, Furusako Shoji
a Biology Laboratory, Discovery Research, Mochida Pharmaceutical Co., LTD. , Jimba , Gotemba , Shizuoka , Japan.
Platelets. 2015;26(8):745-50. doi: 10.3109/09537104.2014.991707. Epub 2014 Dec 30.
Glycoprotein VI (GPVI) plays a critical role in the platelet response to collagen. Clinical studies suggest that the plasma level of soluble GPVI (sGPVI) is a highly specific and useful platelet activation marker. However, many properties of sGPVI have not been fully characterized, such as its sensitivity in detecting platelet activation and its elimination rate from the blood. In this study we established a sandwich enzyme-linked immunosorbent assay for human sGPVI, which cross-reacts to cynomolgus monkey sGPVI, and evaluated the time course of sGPVI production in a cynomolgus monkey model of lipopolysaccharide (LPS)-induced thrombocytopenia. The sGPVI levels in this model were dramatically elevated and returned to baseline by 24 hours after LPS injection, the change was more pronounced than the existing platelet activation biomarker, soluble P-selectin (sP-selectin) levels. The elimination half-life of recombinant human sGPVI was about 2.5 hours following intravenous administration to monkeys. These results suggest that plasma sGPVI closely reflects platelet activation in the bloodstream and has a short half-life. sGPVI would be a useful biomarker for disorders marked by platelet activation and for monitoring anti-platelet therapy.
糖蛋白VI（GPVI）在血小板对胶原蛋白的反应中起关键作用。临床研究表明，可溶性GPVI（sGPVI）的血浆水平是一种高度特异性且有用的血小板活化标志物。然而，sGPVI的许多特性尚未完全明确，例如其在检测血小板活化方面的敏感性以及从血液中的清除率。在本研究中，我们建立了一种针对人sGPVI的夹心酶联免疫吸附测定法，该方法与人猿猴sGPVI发生交叉反应，并在人猿猴脂多糖（LPS）诱导的血小板减少模型中评估了sGPVI产生的时间进程。该模型中的sGPVI水平显著升高，并在LPS注射后24小时恢复至基线，这种变化比现有的血小板活化生物标志物可溶性P-选择素（sP-选择素）水平更为明显。重组人sGPVI静脉注射给猴子后的消除半衰期约为2.5小时。这些结果表明，血浆sGPVI密切反映血流中的血小板活化情况且半衰期较短。sGPVI将成为以血小板活化为特征的疾病以及监测抗血小板治疗的有用生物标志物。
