title: Thrombopoietin increases platelet adhesion under flow and decreases rolling.
abstract: Thrombopoietin (TPO) is known to sensitize platelets to other agonists at 20 ng/ml, and above 100 ng/ml it is an independent activator of aggregation and secretion. In studies with a perfusion chamber, TPO, between 0.01 ng/ml and 1 ng/ml, increased platelet adhesion to surface-coated fibrinogen, fibronectin and von Willebrand Factor (VWF) but not to a collagen-coated surface. Increased adhesion was observed at shear rates of 300/s and 800/s in perfusions with whole blood as well as in suspensions of platelets and red blood cells reconstituted in plasma. The by the cyclooxygenase inhibitor, indomethacin, and the thromboxane A2-receptor blocker, SQ30741, abolished the stimulation by TPO. The effect of TPO was mimicked by a very low concentration (10 nmol/l) of the thromboxane TxA2 analogue, U46619. Real-time studies of platelet adhesion to a VWF-coated surface at a shear of 1000/s showed that about 20% of the platelets were in a rolling phase before they became firmly attached. TPO (1 ng/ml) pretreatment reduced this number to < 5%, an effect again abolished by indomethacin. Thus, TPO potentiates the direct and firm attachment of platelets to surface-coated ligands for alphaIIbbeta3, possibly by increasing the ligand affinity of the integrin.
authors.affiliation: Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors.forename: Erim
authors.initials: E
authors.lastname: Van Os
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Wu
authors.forename: Jos G
authors.initials: JG
authors.lastname: Pouwels
authors.forename: Martin J W
authors.initials: MJ
authors.lastname: Ijsseldijk
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Sixma
authors.forename: Jan Willem N
authors.initials: JW
authors.lastname: Akkerman
authors.forename: Philip G
authors.initials: PG
authors.lastname: De Groot
authors.forename: Gijsbert
authors.initials: G
authors.lastname: Van Willigen
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005340:Fibrinogen; D005353:Fibronectins; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D010477:Perfusion; D010974:Platelet Aggregation / Q000187:drug effects*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D013926:Thrombopoietin / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D014841:von Willebrand Factor
chemical_list: D016861:Cyclooxygenase Inhibitors; D005353:Fibronectins; D017482:Receptors, Thromboxane; D014841:von Willebrand Factor; C054215:SQ 30741; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D005340:Fibrinogen; D013926:Thrombopoietin; D007213:Indomethacin