Integrin alpha 2-deficient mice develop normally, are fertile, but display partially defective platelet interaction with collagen.
The integrin alpha(2)-subunit was ablated in mice by targeted deletion of the ITGA2 gene. alpha(2)-Deficient animals develop normally, are fertile, and reproduce. Surprisingly, no obvious anatomical or histological differences were observed in mutant mice. Besides its significance in tissue morphogenesis, integrin alpha(2)beta(1) has been reported to play a major role in hemostasis by mediating platelet adhesion and activation on subendothelial collagen. To define its role in hemostasis, alpha(2)-deficient platelets were analyzed for their capacity to adhere to and aggregate in response to fibrillar or soluble collagen type I. We show that aggregation of alpha(2)-deficient platelets to fibrillar collagen is delayed but not reduced, whereas aggregation to enzymatically digested soluble collagen is abolished. Furthermore, alpha(2)-deficient platelets normally adhere to fibrillar collagen. However, in the presence of an antibody against GPVI (activating platelet collagen receptor), adhesion of alpha(2)-deficient but not wild type platelets is abrogated. These results demonstrate that integrin alpha(2)beta(1) significantly contributes to platelet adhesion to (fibrillar) collagen, which is further confirmed by the abolished adhesion of alpha(2)-deficient platelets to soluble collagen. Thus, alpha(2)beta(1) plays a supportive rather than an essential role in platelet-collagen interactions. These results are in agreement with the observation that alpha(2)beta(1)-deficient animals suffer no bleeding anomalies.
Holtkötter
Olaf
O
Department of Dermatology, University of Cologne, Cologne, Germany.
Nieswandt
Bernhard
B
Smyth
Neil
N
Müller
Werner
W
Hafner
Martin
M
Schulte
Valerie
V
Krieg
Thomas
T
Eckes
Beate
B
D000818:Animals; D001777:Blood Coagulation; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism* / Q000502:physiology; D005298:Fertility / Q000502:physiology*; D016023:Integrins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D015539:Platelet Activation / Q000502:physiology; D010976:Platelet Count; D038981:Receptors, Collagen
D016023:Integrins; D038981:Receptors, Collagen; D003094:Collagen