| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1992: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
We have studied the action of B-cell stimulatory factors such as IL-4, IL-5, and Il-6 on enriched hematopoietic progenitor cells in serum(plasma)-containing culture as well as serum-free culture. IL-4 alone did not support colony formation. However, in the presence of G-CSF, IL-4 preferentially induced neutrophil colonies. The number of pure neutrophil colonies increased three times over that supported by G-CSF alone. The mapping experiments have clearly shown that IL-4 did not initiate progenitor cell proliferation. Based on these data, IL-4 may induce progenitor cells to become sensitive to G-CSF and thereby induce neutrophil differentiation. In contrast, IL-4 had possible inhibitory effects on macrophage colony formation supported by IL-3 plus M-CSF. Next, we studied the effects of IL-4 on megakaryocyte colony formation from enriched hematopoitic progenitor cells. IL-4 strongly inhibited pure and mixed megakaryocyte colony formation in a dose-dependent manner. Formation of eosinophi
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l colonies, erythroid bursts and erythrocyte-containing mixed colonies was not affected by the addition of IL-4. In addition, the inhibitory effects of IL-4 was also seen in serum-free cultures and in cultures containing highly enriched CD34^+, HLA-DR^+ cells as a target population. Then we studied the effects of IL-l on megakaryocyte colony formation. IL-6 increased the size of pure megakaryocyte colony and significantly augmented the mean diameter and the mean DNA content of megakaryocytes in colonies. These data suggest that IL-6 acts as a terminal maturation factor in megakaryocyte development. On the other hand, IL-9 exerted a significant BPA activity on peripheral blood derived progenitor cells. Also, IL-9 supported a distinct population of BFU-E that are responsive to GM-CSF. Finally, we have studied the effects of stem cell factor(SCF) on highly enriched CD34^+, HLA-DR^+ cells as a target population. SCF synergistically interacted with G-CSF or Epo and induced pure neutrophil colonies or erythroid bursts. In addition, SCF significantly enhanced proliferations of neutrophil colonies and erythroid bursts. To further clarify the interactions of B-cell stimulatory factors and other cytokines, additional works will be required using highly purified progenitors and serum-free cultures. Less
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