Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen.
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.
Nieswandt
B
B
Department of Molecular Oncology, General Surgery, Witten/Herdecke University, 42117 Wuppertal, Germany. nieswand@klinikum-wuppertal.de
Brakebusch
C
C
Bergmeier
W
W
Schulte
V
V
Bouvard
D
D
Mokhtari-Nejad
R
R
Lindhout
T
T
Heemskerk
J W
JW
Zirngibl
H
H
Fässler
R
R
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism*; D002097:C-Reactive Protein / Q000494:pharmacology; D003029:Coagulants / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology; D003435:Crotalid Venoms / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D019012:Integrin beta1 / Q000235:genetics; D016023:Integrins / Q000172:deficiency / Q000378:metabolism*; D037181:Lectins, C-Type; D051379:Mice; D018345:Mice, Knockout; D010973:Platelet Adhesiveness / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D010976:Platelet Count; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D038981:Receptors, Collagen; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical; D013917:Thrombin / Q000494:pharmacology; D013927:Thrombosis / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D003029:Coagulants; D003435:Crotalid Venoms; D019012:Integrin beta1; D016023:Integrins; D037181:Lectins, C-Type; D010980:Platelet Membrane Glycoproteins; D038981:Receptors, Collagen; C098341:platelet membrane glycoprotein VI; C028890:convulxin; D000244:Adenosine Diphosphate; D003094:Collagen; D002097:C-Reactive Protein; D013917:Thrombin