Non-IgE-mediated pulmonary hypersensitivity is mast cell dependent

In murine models for non-IgE-mediated asthma (delayed-type hypersensitivity: DTH) it has been demonstrated that sensitization results in the production of lymphocyte-derived antigen-specific factors. The interaction between these antigen-specific factors and mast cells is thought to play an essential role in DTH. In this study we have examined pulmonary responses in passively sensitized mast cell deficient (WBB6Fl-W/Wv) mice and normal (+/+) littermate controls with dinitrofluorobenzene (DNFB)-specific factor. DNFB-factor was isolated by affinity chromatography from culture supernatant of spleen and lymph node cells from DNFB-sensitized mice. Mice were treated by iv injection with DNFB-factor or vehicle 30 min prior intranasal challenge with dinitrobenzene sulfonic acid (DNS). In vivo bronchoconstriction was measured in a body plethysmographic chamber (BUXCO Inc.). Plasma leakage was assessed by measuring the accumulation of iv injected Evans blue dye in bronchoalveolar lavage fluid (BAL) within 1 h after the challenge. Tracheal reactivity to carbachol in vitro was determined at 3 h. A profound bronchoconstriction was found 0 to 15 min after DNS challenge in normal (+/+) mice sensitized with DNFB-factor when compared to controls. This response was accompanied by an increase in plasma leakage in BAL. Moreover, 3 h after DNS challenge tracheal hyperreactivity was found in DNFB-factor sensitized normal (+/+) mice. In contrast, injection of DNFB-factor and subsequent challenge in WlWv mice failed to induce bronchoconstriction. In addition, no differences were detected in W/Wv mice in plasma leakage into BAL or tracheal reactivity after DNS challenge. In conclusion, our findings show that mast cell contribute significantly to pulmonary responses observed after DNFB-factor sensitization and DNS challenge in mice.