Immature megakaryocytes in the mouse: synergistic response to megakaryocyte potentiator, thrombopoietic stimulatory factor with interleukin 3.

The in vitro biological activities of thrombopoietic stimulating factor, recombinant interleukin 3, and megakaryocyte potentiator from various sources were studied. Growth activities were assessed by the responsiveness of enriched populations of small, immature megakaryocytes to factor preparations by measuring increased numbers of acetylcholinesterase-positive cells and increased cell size as indices of megakaryocyte development. All factors stimulated optimum megakaryocyte growth at high concentrations. Immature megakaryocytes revealed the same responsiveness to titrated amounts of the various factors tested, with similar slopes to the dose-response curves. The activities of both thrombopoietic stimulating factor and megakaryocyte potentiator were additive when suboptimal doses were used. In contrast, low concentrations of recombinant interleukin 3 and thrombopoietic stimulating factor acted synergistically to stimulate an optimal response. The data indicate that at low and perhaps physiologically relevant concentrations, two classes of factors influence murine megakaryocyte development by different but related mechanisms.