| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1993: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1992: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Research Abstract |
1,25-Dihydroxyvitamin D_3 (1,25(OH)_2D_3) was recently shown to promote maturation fo 5-fluorouracil (5FU)-treated bone marrow cells by up-regulating macrophage-clony stimulating factor (M-CSF) receptors in the presence of interleukin 1alphsa (IL-1alpha). In order to reveal how1,25(OH)_2D_3 interacts with clony-stimulation factors and regulates the differentiation of bone marrow progenitor cell population, in the present study, nutural bone marrow cells were isolated from untreated mice and used in alpha-minimum essential medilum supplelmented with 20% heat-inactivated horse serum without added appropriate cytokines. Under the conditions, cells spontaneously differentiated gradually with days of culture, as assessed by epression of macrophage differentiation antigens such as Mac-1 (CD11b) and F4/80. Both M-CSF and granulocyte macrophage-colony stimulating factor (GM-CSF) induced only Mac-1 antigen expression. Simultaneous treatment with M-CSF and 1,25(HD)_2D_3 per se has no effect on the espression for up to 11 days. In addition, successive treatment with 1,25(OH)_2D_3 and M-CSF or GM-CSF dramatically enhanced expression of both antigens or Mac-1 antigen, respectively. Similarly, both simultaneous and successive treatment with 1,25(HD)_2D_3 and M-CSF significantly enhanced phagocytic activity and H_2O_2 production, Whereas successive treatment with 1,25(HD)_2D_3 and GM-CSF significantly enhanced only phagocytic activity. Enzymehistochemical study demonstrated that cells treated simultaneously or successively with 1,25(HD)_2D_3 and M-CSF were strongly positive for nonspecific esterase (NSE), a macrophage-specific maker, and that simultaneous or succesive treatment with 1,25(HD)_2D_3 primes bone marrow progenitor cell populations not only to M-CSF but also to GM-CSF and thereby accelelrates the CSFs-dependent differentiation of the cell
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