Mast cell activation enhances airway responsiveness to methacholine in the mouse

Mast cell-deficient mutant mice and their normal littermates were used to determine whether activation of mast cells by anti-IgE enhances airway responsiveness to bronchoactive ago-nists in vivo. Pulmonary conductance was used as an index of airway response as the mice were challenged with increasing intravenous doses of methacholine (Mch) or 5-hydroxytrypta-mine (5-HT). Mast cell activation with anti-IgE enhanced pul-monary responsiveness to Mch in both types of normal mice (P < 0.0001 by analysis of variance) but not in either genotype of mast cell-deficient mouse. Additionally, anti-IgE pretreatment of genetically mast cell-deficient W / Wv mice whose mast cell deficiency had been repaired by infusion of freshly obtained bone marrow cells or bone marrow-derived cultured mast cells from congenic normal mice led to significant (P < 0.0001) en-hancement of Mch responsiveness. 5-HT responsiveness was not significantly influenced by anti-IgE pretreatment in any of the mice studied. The data support the hypothesis that IgE-me-diated activation of mast cells enhances pulmonary responsive-ness to cholinergic stimulation. (J. Clin. Invest. 1993