Glycoprotein VI but not α2β1 integrin is essential for platelet interaction with collagen

被引:418
作者
Nieswandt, B [1 ]
Brakebusch, C
Bergmeier, W
Schulte, V
Bouvard, D
Mokhtari-Nejad, R
Lindhout, T
Heemskerk, JWM
Zirngibl, H
Fässler, R
机构
[1] Univ Witten Herdecke, Dept Mol Oncol, D-42117 Wuppertal, Germany
[2] Univ Lund, Dept Expt Pathol, S-22185 Lund, Sweden
[3] Maastricht Univ, Dept Biochem, Maastricht, Netherlands
关键词
collagen; Cre; loxP; GPVI; alpha; 2; beta; 1; integrin; platelets;
D O I
10.1093/emboj/20.9.2120
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Platelet adhesion on and activation by components of the extracellular matrix are crucial to arrest posttraumatic bleeding, but can also harm tissue by occluding diseased vessels. Integrin alpha2 beta1 is thought to be essential for platelet adhesion to subendothelial collagens, facilitating subsequent interactions with the activating platelet collagen receptor, glycoprotein VI (GPVI). Here we show that Cre/loxP-mediated loss of pl integrin on platelets has no significant effect on the bleeding time in mice. Aggregation of beta1-null platelets to native fibrillar collagen is delayed, but not reduced, whereas aggregation to enzymatically digested soluble collagen is abolished. Furthermore, beta1-null platelets adhere to fibrillar, but not soluble collagen under static as well as low (150 s(-1)) and high (1000 s(-1)) shear flow conditions, probably through binding of alpha IIb beta3 to von Willebrand factor. On the other hand, we show that platelets lacking GPVI can not activate integrins and consequently fail to adhere to and aggregate on fibrillar as well as soluble collagen. These data show that GPVI plays the central role in platelet-collagen interactions by activating different adhesive receptors, including alpha2 beta1 integrin, which strengthens adhesion without being essential.
引用
收藏
页码:2120 / 2130
页数:11
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