| Budget Amount *help |
¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
At the site of inflammation, adhesion molecules such as ICAM-1, VCAM-1, E- and P-selectins are expressed on the surface of endothelial cells, on the other hand, Mac-1, VLA-4 and sialyl Lewis^x are expressed on the surface of inflammatory cells. These molecules interact each other and play an important roles in traffic of cells from blood vessels to tissue. In this regard, sialyl Lewis^x analogue is hypothesized to suppress the inflammatory responses by inhibiting the binding between selectins and sialyl Lewis^x. To examine this hypothesis, we evaluated the effect of SLX analogue on pathological changes in the experimental mouse model.
After sensitization, we determined the responses of mice with transnasally administered Micropolyspora faeni (Mf), then SLX analogue was delivered by intraperitoneally or administered transnasally. Mice exposed to antigen (positive control) showed the increases of the number of lymphocyte ratio in their bronchoalveolar lavage fluids to compare the controls. In mice treated with sialyl Lewis^x, they were significantly lower than those in positive control. In addition, histological scores of mice treated with sialyl Lewis^x, which were determined according to previous reports, were significantly lower than that of positive control. In addition, expression of E- and P- selectins in endothelial cells of pulmonary arterioles were evaluated with immunohistochemistry, These results suggested that the interaction between selectins, such as E-selectin, and sialyl Lewis^x play a critical role in inflammatory cell infiltration in the lung of mice, and sialyl Lewis^x analogue may be a possible therapeutic drug to suppress pulmonary inflammatory response.
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