|Budget Amount *help
¥5,900,000 (Direct Cost : ¥5,900,000)
Fiscal Year 1992 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 1991 : ¥4,700,000 (Direct Cost : ¥4,700,000)
Mast cell are derived from multipotential hematopoietic stem cells and classified into at least two phenotypically distinct subpopulations; connective tissue-type mast cells (CTMC) and mucosal mast cells (MMC). When normal mouse bone marrow cells were cultured with IL-3, a large number of mast cells ,which were tissue culture equivalents of the MMC subclass, were developed. Mature CTMC purified from mouse peritoneal calls could proliferate in the presence of both IL-3 and IL-4. Stem cell factor (SCF), the ligand for the c-kit tyrosine kinase receptor, demonstrated to act synergistically with a variety of cytokines including IL-3, IL-6, and G-CSF on the development of early hematopoietic progenitors. Although SCF alone failed to induce mast cells from bone marrow lineage negative cells, it stimulated mast cell production in combination with IL-3. Either SCF, IL-3 alone could not induce mast cell colonies from purified mature CTMC, but SCF revealed significant cooperative actions with IL-3, IL-4 or GM-CSF on the proliferation of mouse CTMC in vitro. The anti-c-kit receptor antibody (ACK2) completely blocked the activity of SCF but not of IL-3 on the growth of CTMC. When we cultured human CD34^+ cells purified from cord blood or bone marrow cells in the presence of SCF, human mast cells first detected on 14 days of incubation and increased dramatically after 50 days of culture. More than 90% of the cells in culture with SCF,SCF+IL-6 or SCF+IL-11 were mast cells after 60 days of culture of cord blood CD34^+ cells. IL-3 and GM-CSF significantly inhibited SCF-dependent mast cell proliferation.