MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR (MGDF) MODERATELY ENHANCES IN-VITRO PLATELET-AGGREGATION

Megakaryocyte growth and development factor (MGDF) is a novel cytokine which promotes the development of immature megakaryocytes into platel ets. We tested the hypothesis that MGDF would alter the sensitivity of platelets to aggregating agents as assessed by in-vitro platelet aggr egometry. 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 add ition 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 phosphoryla tion of platelet proteins with apparent molecular weights of 85 kDa an d 130 kDa. From these data we conclude that exogenously added MGDF mod erately increases the sensitivity of platelets to aggregating agents t hrough a mechanism which appears to involve tyrosine phosphorylation o f platelet proteins.