| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
The upper respiratory tract mucosa is an active site for immune response, and various inflammatory responses are observed in the mucosa. However, the mechanism for the onset and persistence of the inflammatory condition is yet controversial. Therefore, we investigated the interaction between antigen presenting cells and T-lymphocyte in the nasal polyps and paranasal sinus mucosa obtained from patients with chronic sinusitis. We immunohistochemically examined the expression of HLA-DR and the costimulators on macrophages in the nasal polyps of patients with chronic sinusitis. We found that some of the macrophages in the submucosal layer of the polyps expressed HLA- DR or one of the costimulators, indicating that a macrophage acts as an APC, expressing both MHC-II and costimulators, and modulates the mucosal immune response. In patients given macrolides, a greater number of CD80-positive macrophages was observed. The percentage of CD80-positive macrophages was negatively correlated with the percentage of infiltrating eosinophils in the polyps. Therefore expression of CD80 may play a key role in mucosal immune response, particularly in eosinophilic inflammation, in a nasal polyp.
Then the expression of HLA-DR, CD54, CD80 and CD86 on cultured human peripheral mononuclear cells following stimulation by interferon-_(IFN-_) and lipopolysaccharides (LPS) was analyzed using flow cytometry in the presence and absence of macrolides. The macrolides tested inhibited the expression of CD54, CD80 and CD86 on cultured monocytes following stimulation by IFN-_ and LPS, while the expression of HLA-DR on monocytes was not affected.
From these results, the expression of HLA-DR and costimulatory molecules may be responsible for the formation of various inflammation including eosinophilic inflammation in the upper respiratory tract, and macrolides may normalize the hyperimmune response and chronic inflammation.
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