|Budget Amount *help
¥1,900,000 (Direct Cost : ¥1,900,000)
Fiscal Year 1994 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1993 : ¥1,000,000 (Direct Cost : ¥1,000,000)
We could not complete the experiments of above theme, because of some difficulties concerning maintenance of T cell clones. Instead, we report herein the results of fundamental experiments of the study. We have successfully made a murine model of antigen-driven pulmonary eosinophilia. Primed mice (BALB/c, 6-8wk old) with ovualbumin (OVA) and alum (three times, 2-wk interval) were challenged with OVA by inhalation (50mg/ml for 20min, 6 days) , yielded 9x10^5/ml Eo in bronchoalveolar lavage fluids (BALF) at 24-hours after the last challenge. Histological analysis revieled peribronchiolar and perivascular cell infiltration of lymphocytes and eosinophils. Recently, thromboxane A2 (TxA2) synthetase inhibitor (Sl) and receptor antagonist (RA) have been developed for the prophylaxis of bronchoconstriction. These compounds can improve pronchial hyperreactivity, indicating that the points of their action seem to be more than bronchoconstriction. To explore their influence on eosinophil (Eo) infiltration, we treated this model mice with OKY-046 (TxA2 Sl ; 100,10,1mg/kg) and S-1452 (TxA2 RA ; 25,2.5,0.25 mg/kg). Treatment with either compound significantly reduced Eo number in BALF in a dose-dependent manner up to-70% at the highest dose. Although we could detect IL-5 neither in BALF nor serum from untreated mice, the production of IL-5 decreased in culture supernatants of OVA plus spleen cells from treated mice with either compound in a dose-dependent manner up to-75% at the highest dose. The production of both interferon-gamma and IL-2 also significantly decreased. The cell differentials and percentages of CD3,4 or 8-positive splenocytes from treated mice were not significantly different from untreated mice. These results suggest that inhibition of TxA2 may reduce not only bronchoconstrictive response but also pulmonary infiltration of eosinophils by inhibiting cytokines production in vivo.