Collagen Response and Glycoprotein VI Function Decline Progressively as Canine Platelets Age in vivo
Collagen Response and Glycoprotein VI Function Decline Progressively as Canine Platelets Age in vivo
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随着犬体内血小板的老化，胶原蛋白反应和糖蛋白 VI 功能逐渐下降
DOI：
10.1055/s-0037-1613245
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发表时间：
2002
影响因子：
6.7
通讯作者：
G. Dale
中科院分区：
文献类型：
--
作者：
L. Alberio;P. Friese;K. Clemetson;G. Dale
临床和实验观察表明，血小板功能随着细胞年龄的增长而迅速恶化。然而，定义年龄依赖性改变的努力只检测到在细胞生命周期后期发生的适度生化变化。在本报告中，我们证明了在犬血小板体内衰老过程中胶原反应发生的两个显著变化：I、III和V型胶原的EC50逐渐增加，以及一群对胶原难降解的衰老血小板的出现。痉挛素（一种胶原受体糖蛋白VI （GPVI）的特异性激动剂）的实验也证明了活性的年龄依赖性下降，并且在天然胶原中观察到无反应性的老年人群的出现。我们的研究表明犬血小板对fitc标记的惊厥素有两种不同的结合水平，并且随着细胞老化，较高的结合水平消失。在这些研究中，发现一只狗（#428）的血小板不仅没有表现出惊厥素反应性的年龄依赖性下降，而且在其正常寿命中保持了高度的惊厥素结合能力。将对照犬的生物素化血小板输注到428号犬中，结果显示，输注的血小板中胶原反应和GPVI功能没有发生预期的变化。这些观察结果表明，犬血小板对胶原蛋白的反应强烈依赖于细胞年龄，并表明这种功能下降至少部分是由于外部介导的改变，可能是GPVI的蛋白水解。这项工作得到了美国国立卫生研究院（GLD）和瑞士国家科学基金会（SSMBS grant， LA; grant 31-52396.97， KJC）的部分资助HL53585和HL68129。这项工作已在国际血栓和止血学会第十八届大会（巴黎，2001年）上发表。
Summary Clinical and experimental observations suggest that platelet function deteriorates quickly with cell age. However, efforts to define agedependent alterations have detected only modest biochemical changes occurring late in the cell life span. In this report, we demonstrate two significant alterations of the collagen response occurring during in vivo aging of canine platelets: a progressive increase in the EC50 for collagen types I, III and V and the emergence of a population of aged platelets which are refractory to collagen. Experiments with convulxin, a specific agonist for the collagen receptor glycoprotein VI (GPVI), also demonstrate an age-dependent decline in activation and the appearance of a non-reactive, aged population as observed with native collagens. Our studies indicate that canine platelets have two distinct binding levels for FITC-labeled convulxin and that the higher binding level disappears upon cell aging. During these studies one dog (#428) was identified whose platelets not only failed to demonstrate an age-dependent decrease in convulxin reactivity but also maintained a high convulxinbinding ability throughout their otherwise normal life span. Transfusion of biotinylated platelets from control dogs into dog #428 showed that the expected changes in collagen response and GPVI function did not occur in the transfused platelets. These observations demonstrate that the canine platelet response towards collagen is strongly dependent upon cell-age and suggest that this functional decline is at least partly due to an extrinsic-mediated alteration, possibly proteolytic, of GPVI. This work was supported in part by grants HL53585 and HL68129 from the National Institutes of Health (GLD) and the Swiss National Science Foundation (SSMBS grant, LA; grant 31-52396.97, KJC). This work has been presented at the XVIII Congress of the International Society on Thrombosis and Haemostasis (Paris, 2001).
通过 P-选择素表达定量，老化血小板对凝血酶的反应受损。
影响因子：
20.3
作者：
Peng,J;Friese,P;Heilmann,E;George,JN;Burstein,SA;Dale,GL
通讯作者：
Dale,GL
影响因子：
20.3
作者：
Alberio, L;Safa, O;Dale, GL
通讯作者：
Dale, GL
来自血小板生成素和白细胞介素 6 治疗的狗的血小板的相对反应性。
影响因子：
20.3
作者：
Peng,J;Friese,P;Wolf,RF;Harrison,P;Downs,T;Lok,S;Dale,GL;Burstein,SA
通讯作者：
Burstein,SA