| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Motoyoshi Yokohama City Univ., Medicine, Assistant Professor, 医学部, 助手 (10295496)
MIYASHITA Akira Yokohama City Univ., Medicine, Associate Professor, 医学部・附属市民総合医療センター, 講師 (40239398)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
Epidemiologically, respiratory viral infections are a major cause of wheezing in infants and adult patients with asthma. Infectious type of asthma may develop after respiratory viral infection, although its mechanism is still unknown. Previously, we demonstrated that infection by influenza A virus enhances sensitization to inhaled antigens and airway responsiveness in mice (JACI 102 ; 732, 1998). In the present study, we studied the mechanism of enhanced sensitization to inhaled antigen, including antigen-presenting cells, in influenza A virus infection.
We applied an antigen (ovalbumin) by aerosol inhalation, because this inhalation sensitization technique may reflect more appropriately the actual route of sensitization in the development of human asthma. BALB/c mice were inoculated intranasally with Influenza A/Guizhou-X/H3N2. Animals were exposed to aerosols of ovalbumin (OVA) during the acute phase of the infection. Two weeks later, airway responsiveness (AR) was increased and both levels of OVA-specific IgE and Th2 cytokines were also rose. Histologically, dendritic cells were observed on the bronchial epithelium and OA-capturing dendritic cells migrated to the regional lymphnodes. OA inhalation during the recovery phase did neither produce OA-specific IgE and migrate dendritic cells to the bronchi. In analysis of cytokines and chemokines during the acute phase of infection, IFN-ν increased upto day 7 postinfection, and TNF-α, MIP-2 and KC increased maximally on day 3. However, Th2 cytokines such as IL-4 and IL-5 did not show any change by viral infection, and also IL-12 did not increase.
Therefore, during the acute phase of viral infection, the dendritic cells appear to the bronchial epithelium and capture inhaled antigens, resulting in type 2 immune response. However, the mechanism of stimulation of the dendritic cells is still unknown.
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