title: Epoprostenol inhibits human platelet-leukocyte mixed conjugate and platelet microparticle formation in whole blood.
abstract: Circulating platelet-leukocyte mixed conjugates and platelet microparticles are potential markers of inflammation in the atherothrombotic disease. Epoprostenol is a synthetic salt of PGI2 (prostacyclin) clinically used in pulmonary hypertension and transplantation as a potent inhibitor of platelet aggregation. In this study the in vitro effect of this drug was investigated on the interaction of platelets with leukocytes and on markers of leukocyte and platelet activation, including platelet microparticle formation. The analyses were performed by flow cytometry on citrated whole blood collected from healthy subjects and challenged by a mixture of collagen-ADP. Preliminarily, the epoprostenol antiplatelet effect was confirmed by both aggregometry and PFA-100 and by evaluation of intraplatelet VASP phosphorylation. Epoprostenol, at nanomolar concentrations, prevented the formation of platelet mixed conjugates with PMN or monocytes, platelet PAC-1 and P-selectin expression and platelet microparticle generation. The reference drugs PGE1, aspirin and the novel ADP-receptor antagonist, cangrelor, were only effective at micromolar concentrations. No effect of epoprostenol was detected on leukocyte activation markers. Our data suggest a possible additional mechanism of action of epoprostenol in reducing the inflammatory cell contribution to pulmonary hypertension and thrombosis.
authors.affiliation: Laboratory of Cell Biology and Pharmacology of Thrombosis, Research Laboratories, Center for High Technology Research and Education in Biomedical Sciences John Paul II, Catholic University, Campobasso, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tamburrelli
authors.forename: Marilena
authors.initials: M
authors.lastname: Crescente
authors.forename: Benedetta
authors.initials: B
authors.lastname: Izzi
authors.forename: Maria
authors.initials: M
authors.lastname: Barisciano
authors.forename: Maria Benedetta
authors.initials: MB
authors.lastname: Donati
authors.forename: Giovanni
authors.initials: G
authors.lastname: de Gaetano
authors.forename: Chiara
authors.initials: C
authors.lastname: Cerletti
mesh_terms: D015415:Biomarkers; D001792:Blood Platelets / Q000473:pathology / Q000648:ultrastructure; D055252:Cell-Derived Microparticles / Q000187:drug effects*; D002478:Cells, Cultured; D011464:Epoprostenol / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors
chemical_list: D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D011464:Epoprostenol