Glycoprotein VI but not alpha 2 beta 1 integrin is essential for platelet interaction with collagen

Platelet adhesion on and activation by components of the extracellular matr ix are crucial to arrest posttraumatic bleeding, but can also harm tissue b y occluding diseased vessels. Integrin alpha2 beta1 is thought to be essent ial for platelet adhesion to subendothelial collagens, facilitating subsequ ent interactions with the activating platelet collagen receptor, glycoprote in VI (GPVI). Here we show that Cre/loxP-mediated loss of pl integrin on pl atelets has no significant effect on the bleeding time in mice. Aggregation of beta1-null platelets to native fibrillar collagen is delayed, but not r educed, whereas aggregation to enzymatically digested soluble collagen is a bolished. Furthermore, beta1-null platelets adhere to fibrillar, but not so luble 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 adhe sion without being essential.