| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
The deposition of immune complexes (IC) induces an acute inflammatory response with tiss* injury. IC-induced inflammation is mediated by inflammatory cell infiltration, a process high* regulated by expression of multiple adhesion molecules. To assess the role of L-selectin ar* intercellular adhesion molecule-1 (ICAM-1) in this pathogenetic process, the cutaneous rever* passive Arthus reaction was examined in mice lacking L-selectin (L-selectin-/-), ICAM-1 (ICAM-1-/* or both (L-selectin/ICAM-1-/-). Edema and hemorrhage, which peaked 4 and 8 hours after * challenge respectively, were significantly reduced in L-selectin-/-, ICAM-1-/-, and L-selectin/ICAM* 1-/- mice compared with wild type littermates. In general, edema and hemorrhage were mo significantly inhibited in ICAM-1-/- mice than in L-selectin-A mice, but were most significant* reduced in L-selectin/ICAM-1-/- mice compared with ICAM-1-/- or L-selectin-/- mice. Decrease edema and hemorrhage correlated with reduced neutrophil and mast cell infiltration in all adhesi* molecule-deficient mice, but leukocyte infiltration was most affected in L-selectin/ICAM-1-/- mic Reduced neutrophil and mast cell infiltration was also observed for all mutant mice in the peritone Arthus reaction. Furthermore, cutaneous tumor necrosis factor-a production was inhibited in ea* deficient mouse, which paralleled the reductions in cutaneous inflammation. These resu* indicate that ICAM-1 and L-selectin cooperatively contribute to the cutaneous Arthus reaction * regulating neutrophii and mast cell recruitment and suggest that ICAM-1 and L-selectin a therapeutic targets for human IC-mediated disease.
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