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The roles of alpha IIb beta 3-mediated outside-in signal transduction, thromboxane A2, and adenosine diphosphate in collagen-induced platelet aggregation. Blood 2003 Apr 01;101(7):2646-51

Date

11/26/2002

Pubmed ID

12446460

DOI

10.1182/blood-2002-05-1363

Scopus ID

2-s2.0-0037512367   61 Citations

Abstract

Collagen-induced activation of platelets in suspension leads to alpha(IIb)beta(3)-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 alpha(IIb)beta(3)-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 alpha(IIb)beta(3)-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 PLC gamma 2, G alpha q, or TxA2 receptors, as well as platelets treated with a protein kinase C inhibitor, Ro31-8220. Thus, activation of alpha(IIb)beta(3) 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.

Author List

Cho MJ, Liu J, Pestina TI, Steward SA, Thomas DW, Coffman TM, Wang D, Jackson CW, Gartner TK

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Diphosphate
Animals
Collagen
Dose-Response Relationship, Drug
GTP-Binding Protein alpha Subunits, Gq-G11
Heterotrimeric GTP-Binding Proteins
Kinetics
Mice
Phospholipase C gamma
Platelet Aggregation
Platelet Glycoprotein GPIIb-IIIa Complex
Signal Transduction
Thromboxane A2
Type C Phospholipases
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5