Regulation of CD40L (CD154) and CD62P (p-selectin) surface expression upon GPIIb-IIIa blockade of platelets from stable coronary artery disease patients.
BACKGROUND
The aim of this study was to further characterize the effect of the antiplatelet agents, aspirin and eptifibatide, on the surface expression of CD40L and CD62P on platelets from patients with stable coronary artery disease.


METHODS
Platelet function was evaluated using standard light transmission aggregometry. Measurements of CD62P and CD40L were carried out by flow cytometry and ELISA assays.


RESULTS
All patients had the expected level of platelet aggregation inhibition in response to 20 muM ADP in the presence of increasing eptifibatide concentrations. Platelet activation by adenosine diphosphate (ADP) or thrombin agonist peptide (TRAP) increased CD62P and CD40L surface density in the presence of aspirin by 1.9 - 2.8 -fold. Aspirin treatment did not prevent either CD62P or CD40L expression. Eptifibatide pretreatment at pharmacologically relevant concentrations blocked agonist-induced increases in CD62P platelet surface density. A marked percentage of platelets still expressed low levels of surface CD62P suggesting slight platelet activation even with potent platelet inhibition. Eptifibatide also blocked agonist-induced increases in CD40L surface expression and decreased the percent of platelets positive for surface CD40L. Decreased expression of CD40L was due to an inhibition of CD40L translocation and not caused by enhanced shedding from the surface, as soluble CD40L (sCD40L). Eptifibatide concentrations that effectively blocked platelet aggregation correlated with total inhibition of increased CD62P and CD40L surface density.


CONCLUSIONS
Blockade of the GPIIb-IIIa receptor on platelets from coronary artery disease patients may have significant bearing on reducing proinflammatory and procoagulant events mediated by CD62P and sCD40L.
Chandler
A Bleakley
AB
University Health Care System, 1348 Walton Way Suite #5100, Augusta, GA 30901, USA. bleakleychandler@mac.com
Earhart
Angela D
AD
Speich
Henry E
HE
Kueter
Teddi J
TJ
Hansen
Jennifer
J
White
Melanie M
MM
Jennings
Lisa K
LK
D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D003327:Coronary Disease / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000077542:Eptifibatide; D006801:Humans; D019007:P-Selectin / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*
D019007:P-Selectin; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D023201:CD40 Ligand; D000077542:Eptifibatide; D001241:Aspirin