| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
To know the role of the nerve system in allergic skin diseases, we investigated the release of histamine, LTB4 and TNFα from skin mast cells in response to substance P, and the mechanism of mast cell-growth and differentiation. Every skin tissues obtained from all human donors by surgical operations released histamine, but tissues of only 34.8% and 80% of the donors released LTB4 and TNFα, respectively in response to substance P. The release of TNFα, but not that of histamine was inhibited either by preincubation of the tissues with steroid or MAP kinase (ERK) inhibitor. We report a case of urticaria, who developed eruptions together with the abnormal brain waves on exercise, perspiration or psychological tensjon, suggesting that abnormal activities of central nerve system could associate with skin allergic reactions
We next studied about the functional heterogeneity, differentiation and growth of skin mast cells, using co-culture system of mouse bone marrow-derived mast cells and NIH-3T3 fibroblasts. When the mast cells were cultured with SCF alone, they released LTB4, but not histamine in response to substance P. On the other hand, when mast cells lacking signaling machinery for c-kit, the receptor for SCF, were cultured with fibroblasts, they released histamine, but not LTB4 in response to substance P. The release of LTB4 from mouse mast cells was inhibited by either steroid, a MAP kinase-inhibitor or an anti-allergic H1-blocker. The release of LTB4 was not correlated to the increase of intracellular Ca^<2+> concentration. These results indicate that the growth and differentiation of skin mast cells were induced by both SCF and non-SCF fibroblast-derived factor.
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