Human eosinophils induce mucin production in airway epithelial cells via epidermal growth factor receptor activation

(E)osinophil recruitment and mucus hypersecretion are characteristic of ast hmatic airway inflammation, but eosinophils have not been shown to induce m ucin production. Because an epidermal growth factor receptor (EGFR) cascade induces MUC5AC mucin in airways, and because EGFR is up-regulated in asthm atic airways, we examined the effect of eosinophils on MUC5AC mucin product ion in NCI-H292 cells (a human airway epithelial. cell line that produces m ucins). Eosinophils were isolated from the peripheral blood of allergic pat ients, and their effects on MUC5AC mucin gene and protein synthesis were as sessed using in situ hybridization and ELISAs. When IL-3 plus GM-CSF or IL- 3 plus IL-5 were added to eosinophils cultured with NCI-H292 cells, MUC5AC mucin production increased; eosinophils or cytokines alone had no effect. E osinophil supernatant obtained by culturing eosinophils with IL-3 plus GM-C SF or IL-3 plus IL-5 also increased MUC5AC synthesis in NCI-H292 cells, an effect that was prevented by selective EGFR inhibitors (AG1478, BIBX1522). Supernatant of activated eosinophils induced EGFR phosphorylation in NCI-H2 92 cells. Supernatant of activated eosinophils contained increased concentr ations, of TGF-a protein (an EGFR ligand) and induced up-regulation, of TGF -alpha expression and release in NCI-H292 cells. A blocking Ab to TGF-a red uced activated eosinophil-induced MUC5AC synthesis in NCI-H292 cells. These results show that activated eosinophils induce mucin synthesis in human ai rway epithelial cells via EGFR activation, and they implicate TGF-a produce d by eosinophils and epithelial cells in the EGFR activation that results i n mucin production in human airway epithelium.