MAST-CELLS MODULATE ALLERGIC PULMONARY EOSINOPHILIA IN MICE

Mast cells are important effector cells in IgE-mediated acute allergic reactions. Mast cells also produce cytokines such as interleukin (IL)-3, IL-4, IL-5, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) that regulate the function of eosinophils and the development of a late-phase inflammatory response to antigen challenge. To evaluate the role of mast cells on the development of IgE-mediated allergic pulmonary eosinophilia in vivo, we compared the eosinophil infiltration into lungs of mast cell deficient mice (WBB6F(1)/J -W/W-v) with their congenic normal littermates (W/W+). Mice were sensitized with alum-precipitated ovalbumin and challenged with aerosolized ovalbumin on day 12 after sensitization. Bronchoalveolar lavage (BAL) fluid, lung tissue biopsies, and blood samples were collected after ovalbumin challenge. Eosinophil numbers in the BAL and lung tissue, lung eosinophil peroxidase (EPO) activity and serum levels of IgE and IgG(1) were measured. In sensitized W/W+ mice, there were increased numbers of eosinophils in the BAL fluid and lung tissue, and EPO levels were increased after ovalbumin challenge. Ovalbumin challenge of sensitized mast-cell-deficient mice produced fewer numbers of eosinophils in the BAL fluid and lungs, and EPO levels were also reduced compared with their challenged congenic littermates. On the other hand, levels of serum IgE and IgG(1) were not different between W/W-v mice and their congenic littermates. Adoptive transfer of cultured bone-marrow-derived mast cells (1 x 10(7) cells) from W/W+ mice into W/W-v mice 4-5 wk before sensitization restored the eosinophilia in the BAL fluid and lung tissue and increased EPO levels in the lung to values that were not significantly different from those seen after antigen challenge in normal littermates. These results identify an important role for mast cells in the eosinophil infiltration into the lungs of allergic mice.