STEM-CELL FACTOR (C-KIT LIGAND) INFLUENCES EOSINOPHIL RECRUITMENT ANDHISTAMINE LEVELS IN ALLERGIC AIRWAY INFLAMMATION

The increased reactivity of mast cells during allergic airway inflamma tion has been linked to several aspects of pulmonary disease. A primar y inducer of mast eel! differentiation, proliferation, and activation has been identified as c-kif ligand or stem cell factor (SCF). In the present study, we used an established murine model of allergic eosinop hilic airway inflammation to examine the role of SCF during an Ag-spec ific airway response. Initial data demonstrates increased SCF protein production at 8 h postchallenge in both lungs and serum of allergen-ch allenged, but not vehicle-challenged, mice. The immunolocalization of SCF in Ag-challenged lungs suggested that macrophage populations were the primary source of SCF, while epithelial cell regions also stained positive. Intense immunohistochemical staining of macrophages in bronc hoalveolar lavage samples recovered from Ag-sensitized mice indicate t hat these cells may be a significant source of SCF in the lungs. Alveo lar macrophages from the airways of normal mice stimulated with either TNF (0,1-10 ng/ml) or IL-4 (10 ng/ml) produced significant levels of SCF. Furthermore, neutralization studies demonstrated that the inhibit ion of airway SCF during allergen challenge significantly decreased eo sinophil, but not neutrophil, infiltration throughout the response. Fu rthermore, when mice were treated with anti-SCF Ab, histamine levels w ere significantly reduced at 8 h postchallenge, the time of significan t SCF production. Together, these data indicate that the production of SCF during Ag-induced lung inflammation by alveolar macrophages can p lay a significant role in the subsequent recruitment of eosinophils, p ossibly via mast cell activation and degranulation.