Effects of thrombopoietin and erythropoietin on platelet production in rebound-thrombocytotic and normal mice.

The effects of thrombopoietin-rich (TSF-rich) kidney cell culture medium and partially purified preparations of human urinary and step I sheep plasma erythropoietin (Ep) on platelet production in mice were determined. After TSF and Ep preparations had been injected into mice in rebound thrombocytosis and into normal mice, the rate of incorporation of Na₂ ³⁵SO₄ into platelets was measured as an index of platelet production. TSF injections caused significant increases in platelet production of all the mice; however, greater effects were observed in rebound-thrombocytotic mice than in normal mice. In rebound-thrombocytotic mice, low dosages of Ep (0.25–1.0 units per mouse) significantly depressed percentage ³⁵S incorporation into platelets. The same low dosage of Ep did not alter platelet production rates in normal mice, but large doses (2.5–5.0 units per mouse) stimulated ³⁵S incorporation into platelets. Thus, these results show that Ep caused different responses in rebound-thrombocytotic and normal mice. Endotoxin, injected in dosages previously shown to be present in Ep, gave responses similar to that of the low dosages of Ep, ie, depressed thrombocytopoiesis in rebound-thrombocytotic mice but had no effect in normal mice. When two foreign proteins were injected in doses similar to the previously tested Ep protein content, platelet production was not stimulated. We conclude, therefore, that the thrombocytopoietic effects of Ep cannot be due to contamination with known humoral factors or foreign proteins.