Expression and function of purinergic receptors in platelets from apheresis-derived platelet concentrates

被引:6
作者
Koessler, Juergen [1 ]
Weber, Katja [1 ]
Koessler, Angela [1 ]
Yilmaz, Pinar [1 ]
Boeck, Markus [1 ]
Kobsar, Anna [1 ]
机构
[1] Univ Wurzburg, Inst Transfus Med & Haemotherapy, Oberduerrbacher Str 6, D-97080 Wurzburg, Germany
关键词
platelet concentrate; storage lesion; purinergic receptors; adenosine diphosphate; aggregation; VASP-PHOSPHORYLATION; STORED PLATELETS; P2Y(12) RECEPTOR; STORAGE; AGGREGATION; CONTRIBUTES; DEFINITION; INHIBITION; ANTAGONIST; ACTIVATION;
D O I
10.2450/2015.0073-15
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background. The storage of platelets affects platelet integrity and functionality, a process named platelet storage lesion (PSL). Reduced adenosine diphosphate (ADP)-induced platelet aggregation is a typical manifestation of PSL. However, the role of ADP receptors in this context has not been evaluated yet. The aim of this study was, therefore, to investigate surface expression and function of the purinergic receptors P2Y1, P2Y12 and P2X1 in stored platelet concentrates. Matetial and methods. Platelets were obtained from venous whole blood and from apheresis-derived platelet concentrates stored for 0, 2 and 5 days. Purinergic receptor expression was measured by flow cytometry and western blot analysis. Receptor function was determined by calcium-induced fluorescence (P2Y1 and P2X1) or by flow cytometric measurement of the platelet reactivity index (P2Y12). Results. The basal surface expression and total content of purinergic receptors remained unchanged throughout storage. After an initial reduction during apheresis, P2X1-mediated calcium flux was maintained, whereas the P2Y1-mediated increase of calcium flux gradually decreased during the course of storage. In contrast, the platelet reactivity index was comparable in freshly obtained and stored platelets. Discussion. The function of the P2Y12 receptor is maintained during storage of apheresis-derived platelet concentrates. However, the impairment of P2X1 and especially of P2Y1 receptor function indicated by decreased receptor-mediated calcium flux is an important mechanism contributing to reduced ADP responsiveness of stored platelets.
引用
收藏
页码:545 / 551
页数:7
相关论文
共 35 条
[1]   Development and Clinical use of Prasugrel and Ticagrelor [J].
Ahmad, Shiraz ;
Storey, Robert F. .
CURRENT PHARMACEUTICAL DESIGN, 2012, 18 (33) :5240-5260
[2]   A brief review of the past and future of platelet P2Y12 antagonist [J].
Barn, Kulpreet ;
Steinhubl, Steven R. .
CORONARY ARTERY DISEASE, 2012, 23 (06) :368-374
[3]   Platelet concentrates derived from buffy coat and apheresis:: biochemical and functional differences [J].
Böck, M ;
Rahrig, S ;
Kunz, D ;
Lutze, G ;
Heim, MU .
TRANSFUSION MEDICINE, 2002, 12 (05) :317-324
[4]  
BOCK M, 1994, HAEMOSTASIS, V24, P230
[5]   The platelet P2Y12 receptor for adenosine diphosphate: congenital and drug-induced defects [J].
Cattaneo, Marco .
BLOOD, 2011, 117 (07) :2102-2112
[6]   Hemostatic and signaling functions of transfused platelets [J].
Cauwenberghs, Sandra ;
van Pampus, Elisabeth ;
Curvers, Joyce ;
Akkerman, Jan-Willem N. ;
Heemskerk, Johan W. M. .
TRANSFUSION MEDICINE REVIEWS, 2007, 21 (04) :287-294
[7]   Decreased responsiveness and development of activation markers of PLTs stored in plasma [J].
Curvers, J ;
van Pampus, ECM ;
Feijge, MAH ;
Rombout-Sestrienkova, E ;
Giesen, PLA ;
Heemskerk, JWM .
TRANSFUSION, 2004, 44 (01) :49-58
[8]  
DIMINNO G, 1982, BLOOD, V59, P563
[9]  
FEINBERG H, 1988, BLOOD, V72, P766
[10]   Monitoring of clopidogrel action: Comparison of methods [J].
Geiger, J ;
Teichmann, L ;
Grossmann, R ;
Aktas, B ;
Steigerwald, U ;
Walter, U ;
Schinzel, R .
CLINICAL CHEMISTRY, 2005, 51 (06) :957-965