Platelet glycoprotein V binds to collagen and participates in platelet adhesion and aggregation

被引:107
作者
Moog, S
Mangin, P
Lenain, N
Strassel, C
Ravanat, C
Schuhler, S
Freund, M
Santer, M
Kahn, M
Nieswandt, B
Gachet, C
Cazenave, JP
Lanza, F
机构
[1] Etab Francais Sang Alsace, INSERM U 311, F-67065 Strasbourg, France
[2] Univ Penn, Philadelphia, PA 19104 USA
[3] Univ Witten Herdecke, Klinikum Wuppertal, Wuppertal, Germany
关键词
D O I
10.1182/blood.V98.4.1038
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Glycoprotein V (GPV) is a subunit of the platelet GPlb-V-IX receptor for von Willebrand factor and thrombin. GPV is cleaved from the platelet surface during activation by thrombin, but its role in hemostasis is still unknown. It is reported that GPV knockout mice had a decreased tendency to form arterial occluding thrombi in an intravital thrombosis model and abnormal platelet interaction with the subendothellum. In vitro, GPV-deficient platelets exhibited defective adhesion to a collagen type I-coated surface under flow or static conditions. Aggregation studies demonstrated a decreased response of the GPV-deficient platelets to collagen, reflected by an increased lag phase and reduced amplitude of aggregation. Responses to adenosine diphosphate, arachidonic acid, and the thromboxane analog U46619 were normal but were enhanced to low thrombin concentrations. The defect of GPV null platelets made them more sensitive to inhibition by the anti-GPVI monoclonal antibody (mAb) JAQ1, and this was also the case in aspirin- or apyrase-treated platelets. Moreover, an mAb (V.3) against the extracellular domain of human GPV selectively inhibited collagen-induced aggregation in human or rat platelets. V.3 injected in rats as a bolus decreased the ex vivo collagen aggregation response without affecting the platelet count. Finally, surface plasmon resonance studies demonstrated binding of recombinant soluble GPV on a collagen-coupled matrix. In conclusion, GPV binds to collagen and appears to be required for normal platelet responses to this agonist. (C) 2001 by The American Society of Hematology.
引用
收藏
页码:1038 / 1046
页数:9
相关论文
共 52 条
[1]   Binding of purified 14-3-3 ζ signaling protein to discrete amino acid sequences within the cytoplasmic domain of the platelet membrane glycoprotein Ib-IX-V complex [J].
Andrews, RK ;
Harris, SJ ;
McNally, T ;
Berndt, MC .
BIOCHEMISTRY, 1998, 37 (02) :638-647
[2]   COLLAGEN INCREASES CYTOPLASMIC FREE CALCIUM IN HUMAN-PLATELETS [J].
ARDLIE, NG ;
GARRETT, JJ ;
BELL, LK .
THROMBOSIS RESEARCH, 1986, 42 (02) :115-124
[3]  
Azorsa DO, 1999, THROMB HAEMOSTASIS, V81, P131
[4]  
Barnes M J, 1998, Curr Opin Hematol, V5, P314, DOI 10.1097/00062752-199809000-00002
[5]  
BERNDT MC, 1981, J BIOL CHEM, V256, P59
[6]  
BIENZ D, 1986, BLOOD, V68, P720
[7]  
CAZENAVE JP, 1983, ANN BIOL CLIN-PARIS, V41, P167
[8]   The platelet collagen receptor glycoprotein VI is a member of the immunoglobulin superfamily closely related to FcαR and the natural killer receptors [J].
Clemetson, JM ;
Polgar, J ;
Magnenat, E ;
Wells, TNC ;
Clemetson, KJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (41) :29019-29024
[9]   Glycoprotein (GP) Ib-IX-transfected cells roll on a von Willebrand factor matrix under flow - Importance of the GPIb/actin-binding protein (ABP-280) interaction in maintaining adhesion under high shear [J].
Cranmer, SL ;
Ulsemer, P ;
Cooke, BM ;
Salem, HH ;
de la Salle, C ;
Lanza, F ;
Jackson, SP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (10) :6097-6106
[10]   DISTURBED PLATELET-AGGREGATION TO COLLAGEN ASSOCIATED WITH AN ANTIBODY AGAINST AN 85-KD TO 90-KD PLATELET GLYCOPROTEIN IN A PATIENT WITH PROLONGED BLEEDING-TIME [J].
DECKMYN, H ;
VANHOUTTE, E ;
VERMYLEN, J .
BLOOD, 1992, 79 (06) :1466-1471