| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1987: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1986: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Research Abstract |
P388Dl cells, a macrophage (Mo) cell line, cultured after stimulation by lipopolysaccharide (LPS), produced a glucocorticoid (GC)-dependent hemopoietic activity. The activity, when coexistent with hydrocortisone (HCS), increased number of granulocyte (Gr) colonies 2-3 times more than that formed by CSF alone. HCS scarcely increased the number of Gr colonies stimulated with CSF. We designated this activity as GC-dependent mylopotentiator (GDMP). GDMP activity was partially purified by FPLC using Superose 12 and Mono Q columns. The molecular weight of GDMP was calculated as about 55K daltons. GDMP activity was distinct from CSF, interleukin 1 (IL 1), tumor necrosis factor (TNF) found in the culture supernatant. GDMP was associated with the activity inducing differentiation of myeloleukemic Ml cells in the presence of HCS. Cell size distribution of colony forming cells of bone marrow was investigated by velocity sedimentation apparatus and particular cell populations, responsive to GDMP a
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nd HCS, were found in two restricted regions of sedimentation rate, 4.1mm/hr and 4.8-5.1 mm/hr. It can be considered that the progenitor cell populations, responding to GDMP and HCS, participates as a source of supply of mature Gr. The activity inducing differentiation of Ml cells and GDMP activity were absorbed with Ml cells preincubated with HCS, but not by the cells preincubated with medium alone. HCS may have induced GDMP receptor on Ml cells and the Ml cells were differentiated by GDMP. Thus, both normal Gr precursor cells and myeloid leukemic cells seemed to be differentiated by GDMP and HCS by the same mechanism. Serum GDMP activity was found in mouse sera 2-3 hr after i.v. injection of LPS and declined 5 hr later.
These results suggest that GDMP is involved in the regulation of Gr production in the presence of GC. It seems likely that GDMP is responsible for the responsible for the replenishment of Gr in inflammation. A high level of HCS in an inflammatory state may accelerate expression of GDMP receptor on the progenitor cells. Less
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