Evidence for local eosinophil differentiation within allergic nasal mucosa: Inhibition with soluble IL-5 receptor

Eosinophil differentiation occurs within the bone marrow in response to eos inopoietic cytokines, particularly IL-5. Recently, however, eosinophil prec ursors (CD34/IL-5R alpha(+) cells) and IL-5 mRNA(+) cells have been identif ied within the lungs of asthmatics, indicating that a population of eosinop hils may differentiate in situ, In this report, we examined the presence of eosinophil precursors within allergic nasal mucosa and examined whether th ey undergo local differentiation following ex vivo stimulation. We cultured human nasal mucosa obtained from individuals with seasonal allergic rhinit is with either specific allergen, recombinant human IL-5 (rhIL-5), or aller gen + soluble IL-5R alpha (sIL-5R alpha), shown to antagonize IL-5 function . Simultaneous immunocytochemistry and in situ hybridization demonstrated t hat there were fewer cells coexpressing CD34 immunoreactivity and IL-5R alp ha mRNA following culture with allergen or rhIL-5, compared with medium alo ne. Immunostaining revealed that the number of major basic protein (MBP) im munoreactive cells (eosinophils) was higher within tissue stimulated with a llergen or rhIL-5, compared with unstimulated tissue, In situ hybridization detected an increase in IL-5 mRNA+ cells in sections from tissue cultured with allergen, compared with medium alone. These effects were not observed in tissue cultured with a combination of allergen and sIL-5R alpha. Colocal ization analysis indicated this expression to be mainly, but not exclusivel y, T cell (44%) and eosinophil (10%) derived. Our findings suggest that a s ubset of eosinophils may differentiate locally within allergic nasal mucosa , in what appears to be a highly IL-5-dependent fashion, and imply that thi s process might be regulated in vivo by endogenous production of sIL-5R alp ha.