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*
Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada;
Notre-Dame Hospital, Montreal, Quebec, Canada;
School of Medicine, University of Southampton, Southampton, United Kingdom;
§
Flanders Interuniversity Institute for Biotechnology, University of Ghent, Ghent, Belgium; and
¶
Pulmonary Research Group, University of Alberta, Edmonton, Alberta, Canada
Eosinophil differentiation occurs within the bone marrow in
response to eosinopoietic cytokines, particularly IL-5. Recently,
however, eosinophil precursors (CD34/IL-5R
+ cells) and
IL-5 mRNA+ cells have been identified within the lungs of
asthmatics, indicating that a population of eosinophils may
differentiate in situ. In this report, we examined the presence of
eosinophil precursors within allergic nasal mucosa and examined whether
they undergo local differentiation following ex vivo stimulation. We
cultured human nasal mucosa obtained from individuals with seasonal
allergic rhinitis with either specific allergen, recombinant human IL-5
(rhIL-5), or allergen + soluble IL-5R
(sIL-5R
), shown to
antagonize IL-5 function. Simultaneous immunocytochemistry and in situ
hybridization demonstrated that there were fewer cells coexpressing
CD34 immunoreactivity and IL-5R
mRNA following culture with allergen
or rhIL-5, compared with medium alone. Immunostaining revealed that the
number of major basic protein (MBP) immunoreactive cells (eosinophils)
was higher within tissue stimulated with allergen 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
.
Colocalization analysis indicated this expression to be mainly, but not
exclusively, T cell (44%) and eosinophil (10%) derived. Our findings
suggest that a subset of eosinophils may differentiate locally within
allergic nasal mucosa, in what appears to be a highly IL-5-dependent
fashion, and imply that this process might be regulated in vivo by
endogenous production of sIL-5R
.
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