title: Megakaryocyte growth and development factor (MGDF) moderately enhances in-vitro platelet aggregation.
abstract: Megakaryocyte growth and development factor (MGDF) is a novel cytokine which promotes the development of immature megakaryocytes into platelets. We tested the hypothesis that MGDF would alter the sensitivity of platelets to aggregating agents as assessed by in-vitro platelet aggregometry. Platelet aggregation in the presence or absence of MGDF was tested with single doses of clinically relevant aggregating agents. A dose-dependent enhancement of the aggregation response to epinephrine was noted in MGDF treated platelets. When a range of concentrations of ADP were used to generate an aggregation dose-response curve, the addition of MGDF to platelet rich plasma shifted the dose response curve to the left. The effect of MGDF on platelet aggregation was partially prevented by the coincubation of platelets with a soluble form of the receptor for MGDF, the extracellular domain of c-mpl. In addition, we demonstrate that exogenous MGDF is able to induce tyrosine phosphorylation of platelet proteins with apparent molecular weights of 85 kDa and 130 kDa. From these data we conclude that exogenously added MGDF moderately increases the sensitivity of platelets to aggregating agents through a mechanism which appears to involve tyrosine phosphorylation of platelet proteins.
authors.affiliation: Department of Pharmacology, Amgen, Inc., Thousand Oaks, California 91320, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Toombs
authors.forename: C H
authors.initials: CH
authors.lastname: Young
authors.forename: J A
authors.initials: JA
authors.lastname: Glaspy
authors.forename: B C
authors.initials: BC
authors.lastname: Varnum
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000704:Analysis of Variance; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D018121:Receptors, Cytokine / Q000502:physiology*; D013926:Thrombopoietin / Q000008:administration & dosage / Q000502:physiology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D018121:Receptors, Cytokine; D014443:Tyrosine; D000244:Adenosine Diphosphate; D013926:Thrombopoietin