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

2003; Elsevier BV; Volume: 101; Issue: 7 Linguagem: Inglês

10.1182/blood-2002-05-1363

1528-0020

Moon J. Cho, Junling Liu, Tamara I. Pestina, Shirley A. Steward, Dennis W. Thomas, Thomas M. Coffman, Demin Wang, Carl W. Jackson, T. Kent Gartner,

Antiplatelet Therapy and Cardiovascular Diseases

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.