Objective To demonstrate whether heparin could act synergically with thrombopoietin (TPO) instimulating megakaryocytopoiesis and thrombopoiesis. Methods Megakaryocytic leukemia cell line M- 07e,human cord blood CD34+ cells and Balb/c mice were used for studies. The effectS of hoparin and/or TPO onmegakaryocytopoiesis and thrombopoiesis were studied by [ 3H ] - TdR incoroperation assay, CFU- MK plasmicsemi- solid culture and experiment in Balb/c mice in vivo. In addition, M- 07e cells were used as targets tofurther investigate the possible molecular mechanism by which heparin might act synergically with TPO throughNorthern and Western blot analyses. Results Heparin can act synergically with TPO in stimulating theproliferation of leukemia cell line M- 07e, growth of CFU- MK from human cord blood CD34+ cells andmegakaryocytopoiesis and thrombopoiesis in vivo in mice, possibly by antagonizing downregulation of c- mplexpression by TPO at the level of mRNA transcription, and increasing the phosphotyrosine content Of Jak2,triggered by TPO. Conclusion Heparin participated in positive regulation of megakaryocytopoiesis andthrombopoiesis by enhancing the megakaryocytopoietic activities of TPO, and the mechanism of which might beinvolved in the modification of the molecules c- mpl and Jak2 on the way of signal transduction triggered by TPO.
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