The roles of αIIbβ3-mediated outside-in signal transduction, thromboxane A2, and adenosine diphosphate in collagen-induced platelet aggregation

MJ Cho, J Liu, TI Pestina, SA Steward… - Blood, The Journal …, 2003 - ashpublications.org
MJ Cho, J Liu, TI Pestina, SA Steward, DW Thomas, TM Coffman, D Wang, CW Jackson…
Blood, The Journal of the American Society of Hematology, 2003ashpublications.org
Collagen-induced activation of platelets in suspension leads to αIIbβ3-mediated outside-in
signaling, granule release, thromboxane A2 (TxA2) production, and aggregation. Although
much is known about collagen-induced platelet signaling, the roles of TxA2 production,
adenosine diphosphate (ADP) and dense-granule secretion, and αIIbβ3-mediated outside-
in signaling in this process are unclear. Here, we demonstrate that TxA2 and ADP are
required for collagen-induced platelet activation in response to a low, but not a high, level of …
Collagen-induced activation of platelets in suspension leads to αIIbβ3-mediated outside-in signaling, granule release, thromboxane A2 (TxA2) production, and aggregation. Although much is known about collagen-induced platelet signaling, the roles of TxA2 production, adenosine diphosphate (ADP) and dense-granule secretion, and αIIbβ3-mediated outside-in signaling in this process are unclear. Here, we demonstrate that TxA2 and ADP are required for collagen-induced platelet activation in response to a low, but not a high, level of collagen and that αIIbβ3-mediated outside-in signaling is required, at least in part, for this TxA2 production and ADP secretion. A high level of collagen can activate platelets deficient in PLCγ2, Gαq, or TxA2 receptors, as well as platelets treated with a protein kinase C inhibitor, Ro31-8220. Thus, activation of αIIbβ3 in response to a high level of collagen does not require these signaling proteins. Furthermore, a high level of collagen can cause weak TxA2 and ADP-independent aggregation, but maximal aggregation induced by a high level of collagen requires TxA2 or secretion.
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