EFFECTS OF RECOMBINANT HUMAN MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR ON PLATELET ACTIVATION

The c-Mpl receptor for thrombopoietin and its recombinant related prot ein, the megakaryocyte growth and development factor (MGDF), is also e xpressed on circulating platelets. In the present study we evaluated t he effect of MGDF on platelet aggregation in platelet-rich plasma (PRP ) and in whole blood. The results obtained indicate that MGDF by itsel f did not affect platelet aggregation. However, when added before othe r agonists such as adenosine diphosphates (ADP), epinephrine (EPI), an d thrombin (THR), it rendered platelets more sensitive. This ''priming '' effect of MGDF was dependent on the dose and on the time of platele t preincubation, and it occurred both in PRP and in whole-blood platel et aggregation. MGDF also ''primed'' the release of adenosine triphosp hates and the production of thromboxane B-2 by platelets stimulated wi th ADP, EPI, and THR. When added 15 seconds after the preincubation of platelets with subthreshold concentrations of ADP, EPI, and THR, MGDF exhibited a synergism with these agonists. Moreover, we observed a '' priming'' effect of MGDF on the phosphorylation of p-42 mitogen-activa ted protein kinase promoted by ADP, EPI, and THR. These observations s uggest that thrombopoietin may play a physiologic role in modulating t he response of platelets to several stimuli and thereby their hemostat ic potential. (C) 1996 by The American Society of Hematology.