The roles of alpha IIb beta 3-mediated outside-in signal transduction, thromboxane A2, and adenosine diphosphate in collagen-induced platelet aggregation.
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.
Cho
Moon J
MJ
Department of Microbiology and Molecular Cell Sciences, University of Memphis and the Division of Experimental Hematology, St Jude Children's Research Hospital, Memphis, TN, USA.
Liu
Junling
J
Pestina
Tamara I
TI
Steward
Shirley A
SA
Thomas
Dennis W
DW
Coffman
Thomas M
TM
Wang
Demin
D
Jackson
Carl W
CW
Gartner
T Kent
TK
D000244:Adenosine Diphosphate / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D003094:Collagen / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins; D007700:Kinetics; D051379:Mice; D051966:Phospholipase C gamma; D010974:Platelet Aggregation / Q000187:drug effects*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000502:physiology*; D015398:Signal Transduction; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000502:physiology*; D010738:Type C Phospholipases
D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins