| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Eosinophils and mast cells are important inflammatory cells in allergic irflammation. Adhesion molecules play a crucial role in activation and migration of various cells of allergic inflammation. In addition to these molecules, chemokines such as eotaxin and IL-8 are detected in inflammatory foci, and induce accumulation of inflammatory cells. In our previous studies, we reported that Adhesion molecules and chemokines regulate the eosinophil functions. In contrast to eosinophfls, It remains unclear whether these molecules are expressed on mast cells and affect mast cell functions. First, we examined Ihe expression of adhesion molecules on mast cells based on the results of eosmophils. Purified from cord blood mononuclear cells were cultured wife IL-6 and stromal cel factor, and these cells then differentiated into mast cells. The mast cells expressed ICAM-1, CD11b, CD11a, CD18 and CD49d, and not VCAM-1, Furthennore, ICAM-1 expression on mast cefls was induced by PMA, and reduced by dex
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amethasone. In addition to expression of adhesion molecules, we also determined the expression of chemokine receptor on mast cells. Our result showed CXCR1 and CXCR2 were expressed on mast cells. However we did not detect CCR3 expression on the surface and CCR3 mRNA in mast cells. Moreover, we examined whether CXCR1 and CXCR2 expression were functional. IL-8, the ligand lor CXCR1 and CXCR2 induced Ca influx and chemotaxis. We also determined the regulation of CCR3 expression on eosinophils. PMA and eosinophil active cytokines not affect the CCR3 expression on eosmophils. In addition, no difference between eosinophils from allergic patients and those of healthy subjects were observed.
Recently, we reported the expression and roles of epithelial OCR3. Interestingly, we found that the epithelial CCR3 signaling was largely involved in one of growth factor receptor such as epidermal growth factor receptor (EGFR) like neuron growth factor receptor (NGFR). Based on present results, we further have examined the regulation of chernokine receptor and adhesion molecules expressions on mast cells by cytokines, chemokines and growth foctor such as neuron growth factor. Less
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