title: Clopidogrel, but not abciximab, reduces platelet leukocyte conjugates and P-selectin expression in a human ex vivo in vitro model.
abstract: Formation of platelet-leukocyte aggregates (PLA) through the CD62 ligand is an important mechanism by which leukocytes contribute to thrombosis and inflammation. We investigated the formation of PLA in human subjects after stimulation with thrombin receptor activating peptide and adenosine diphosphate (ADP) after treatment with clopidogrel and after in vitro application of the platelet glycoprotein IIb/IIIa complex antagonist abciximab. Expression of CD62 was significantly reduced 30% to 50% with clopidogrel, depending on the type and concentration of the inducer, but addition of abciximab led to a significant approximately 30% increase in CD62 expression when platelets were stimulated by ADP. Formation of PLA decreased significantly with clopidogrel to 55% to 75% of the baseline value, whereas addition of abciximab caused a significant increase in PLA in ADP-stimulated samples before but not after administration of clopidogrel. The increase in formation of PLA after in vitro addition of abciximab was not paralleled by a decrease in platelet microaggregates and is therefore presumed not caused by enhanced availability of platelets. To our knowledge, this is the first report showing that clopidogrel reduces formation of PLA. The findings also suggest intersection between an "outside-in" signal generated by abciximab and stimulation of platelet P2T(12) purinergic receptors that augments degranulation and increases formation of PLA but is inhibited by clopidogrel.
authors.affiliation: Institute of Clinical Pharmacology, University Hospital.
authors.forename: Ute
authors.initials: U
authors.lastname: Klinkhardt
authors.forename: Jochen
authors.initials: J
authors.lastname: Graff
authors.forename: Sebastian
authors.initials: S
authors.lastname: Harder
mesh_terms: D000077284:Abciximab; D000328:Adult; D000704:Analysis of Variance; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000187:drug effects*; D000077144:Clopidogrel; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D008297:Male; D019007:P-Selectin / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007140:Immunoglobulin Fab Fragments; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077144:Clopidogrel; D013988:Ticlopidine; D000077284:Abciximab