Antigen-stimulated contraction and release of chemical mediators were examined in saline- or Sephadex-treated rat lung parenchymal strips. Sephadex treatment caused eosinophilia in the blood and the lung tissue. Antigen challenge of the isolated parenchymal strips in Sephadex-treated rat was followed by passive sensitization, resulted in an augmented contraction and elevated releases of thromboxane (TX) B₂ and peptide-leukotrienes (p-LTs) in bath fluid compared with those of saline-treated control. Although 5-hydroxytryptamine (5-HT) and histamine were significantly released after antigen challenge, the levels were not different between saline- and Sephadex-treated groups. DP-1904, a selective thromboxane synthetase inhibitor, and methysergide but not atropine significantly reduced the augmented contraction and inhibited the elevated TXB₂ release in the Sephadex-treated group. Similar increased contraction and the elevated TXB₂ release above were observed when Sephadex-treated rat lung strips were stimulated by exogenous 5-HT and LTD₄. These augmented contractions were closely correlated with the increase in TXB₂ level (r = 0.83; p < 0.01). In addition, contraction to U-46619, a thromboxane mimetic, was significantly greater in Sephadex-treated rat lung strips. Our results indicate that the ability of Sephadex-treated rat lung tissue to synthesize newly generated mediators such as TXA₂ and p-LTs is increased, and the spasmogenic susceptibility of the lung tissue to TXA₂ itself is modified by Sephadex treatment, suggesting these are due to the augmented contraction in an established hyperresponsiveness state induced by Sephadex.

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