Study on the regulation mechanism of megakaryocyte and thrombo-cytopoiesis

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Megakaryocytopoiesis in essential thrombocythemia (ET) and polycythemia vera (PV)To characterize abnormal megakaryocytopoiesis and thrombopoiesis in ET and PV, bone marrow megakaryocytic progenitors (CFU-MK) were cultured in a methylcellulose system containg human plasma. Most of the ET patients and about two-thirds of the PV patients studied revealed spontaneous CFU-MK colony growth in the absence of stimulator (PHA-LCM). The number of CFU-MK in ET and PV was significantly increased than that of the control subjects. CFU-MK from ET and PV gave rise to larger number of megakaryocytes per each colony compared to the control subjects. Among PV pateints, those who showed spontaneous CFU-MK were associated with an increased megakaryocyte number number on marrow biopsy specimen and thrombocytosis. Patients with reactive thrombocytosis showed no spontaneous CFU-MK growth, similar to the contro subjects. The data suggested that the abnormally incresed number of megakaryocytes and resultant th … More rombocytosis is, at least partly, due to such abnormal CFU-MK population (spontaneous CFU-MK; autonomous or highly sensitive population to the stimulator). Reactive thrombocytosis may be due to some stimuli on post-CFU-MK compartment (possibly due to incresed thrombopoietin).Efect of various pure growth factors on murine megakaryocytopoiesisThe effects of erythropoietin and IL-3 on murine megakaryocytopoiesis in vitro have been previously demonstrated. This time, we studied the effect of GM-CSF (mouse recombinant) on murine megakaryocytopoiesis in vitro and in vivo. The effect of IL-6 (human, recombinant) was also studied.GM-CSF stimulated CFU-MK as well as CFU-GM colony formation in serum depletedagar culture. GM-CSF also increased the size of megakaryocytes and acetylcholinesterase activity of megakarocytes in liquid culture. The effect was found direct using a single megakaryocyte cylture with or without GM-CSF. When injected in vivo (1 ug twice a day, each mouse, for 6 days), two fold increase of granuloctes was observed. CFU-MK numbers in bone marrow and platelet level were not changed.Using the same culture systems, UL-6 was found to promote the maturation but not proliferation of murine megakaryocytes. The effect was direct. The in vivo role of IL-6 remains to be studied. Less