HEMATOLOGIC EFFECTS OF STEM-CELL FACTOR (SCF) AND LEUKEMIA INHIBITORYFACTOR (LIF) IN-VIVO - LIF-INDUCED THROMBOCYTOSIS IN SCF-PRIMED MICE

Stem cell factor (SCF) administered as daily bolus injections in dose- response experiments in mice causes a progressive and dramatic dose-de pendent panleukocytosis characterized by neutrophilia, eosinophilia, m onocytosis, and lymphocytosis. SCF causes circulating platelet numbers to be dose-dependently increased after 2 weeks of daily injections. L eukemia inhibitory factor (LIF) administered as daily bolus injections in mice causes a peripheral leukopenia that is largely due to periphe ral lymphopenia. LIF causes thrombocytosis peaking after approximately 1 w. Coinjection of SCF and LIF for 1 to 2 wk in mice does not cause a much greater thrombocytosis than the maximum thrombocytosis achievab le with SCF or LIF alone. On the other hand, daily injection of SCF fo r 5 days followed by daily injection of LIF for 5 to 6 d in mice cause s a very substantial increase in platelets that was lineage-specific i n terms of not being accompanied by a generalized leukocytosis. In con trast, only a very modest thrombocytosis was noted in SCF-primed LIF-t reated rats. LIF causes a large increase in the cytoplasmic volume of splenic megakaryocytes in mice, but not in rats. In conclusion, SCF-in duced priming followed by LIF-induced maturation of megakaryocytes cau ses a substantial selective increase in the numbers of circulating pla telets in mice.