Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen.

B. Nieswandt, C. Brakebusch, W. Bergmeier, V. Schulte, D. Bouvard, R. Mohtari-Nejad, T. Lindhout, J.W.M. Heemskerk, H. Zimgibl, R. Fassler

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Abstract

EMBO J 2001 May 1;20(9):2120-30 Related Articles, Books, LinkOut


Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen.

Nieswandt B, Brakebusch C, Bergmeier W, Schulte V, Bouvard D, Mokhtari-Nejad R, Lindhout T, Heemskerk JW, Zirngibl H, Fassler R.

Department of Molecular Oncology, General Surgery, Witten/Herdecke University, 42117 Wuppertal, Germany. nieswand@klinikum-wuppertal.de

Platelet adhesion on and activation by components of the extracellular matrix are crucial to arrest post-traumatic bleeding, but can also harm tissue by occluding diseased vessels. Integrin alpha2beta1 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 beta1 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 alphaIIbbeta3 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 alpha2beta1 integrin, which strengthens adhesion without being essential.

Original languageEnglish
Pages (from-to)2120-2130
Number of pages11
JournalThe Embo Journal
Volume20
DOIs
Publication statusPublished - 1 Jan 2001

Cite this

Nieswandt, B., Brakebusch, C., Bergmeier, W., Schulte, V., Bouvard, D., Mohtari-Nejad, R., Lindhout, T., Heemskerk, J. W. M., Zimgibl, H., & Fassler, R. (2001). Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen. The Embo Journal, 20, 2120-2130. https://doi.org/10.1093/emboj/20.9.2120