Title: Activation of alpha(IIb)beta(3) is a sufficient but also an imperative prerequisite for activation of alpha(2)beta(1) on platelets
Authors: Van de Walle, Gerlinde R
Schoolmeester, Anne
Iserbyt, Brecht
Cosemans, Judith M E M
Heemskerk, Johan W M
Hoylaerts, Marc
Nurden, Alan
Vanhoorelbeke, Karen
Deckmyn, Hans # ×
Issue Date: Jan-2007
Publisher: Amer soc hematology
Series Title: Blood vol:109 issue:2 pages:595-602
Abstract: Platelet integrins alpha2beta1 and alphaIIbbeta3 play critical roles in platelet adhesion and thrombus formation after vascular injury. On resting platelets, both integrins are in a low affinity state. However, agonist stimulation results in conformational changes that enable ligand binding that can be detected with conformation dependent monoclonal antibodies (mAbs). By using such conformation dependent mAbs, we could demonstrate that activation of integrin alphaIIbbeta3 is not only sufficient, but also a prerequisite for alpha2beta1 activation. Compared to platelets in plasma, stimulation of washed platelets resulted in only a minor activation of alpha2beta1, as detected with the activation-sensitive mAb IAC-1. Addition of fibrinogen to stimulated washed platelets greatly potentiated activation of this integrin. Also, treatment of alphaIIbbeta3 with the ligand-mimetic peptide RGDS, resulting in outside-in signaling, led to a powerful alpha2beta1 activation, even in the absence of overall platelet activation, involving tyrosine kinase activity but no protein kinase C activation. The absolute necessity of alphaIIbbeta3 for proper alpha2beta1 activation on platelets was demonstrated by using the alphaIIbbeta3 antagonist aggrastat, which was able to completely abolish alpha2beta1 activation, both under static and flow conditions. Additionally, analogous experiments with Glanzmann platelets, lacking alphaIIbbeta3, confirmed the indispensability of alphaIIbbeta3 for alpha2beta1 activation.
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Chemistry, Campus Kulak Kortrijk
Interdisciplinary Research Facility Life Sciences, Campus Kulak Kortrijk
× corresponding author
# (joint) last author

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