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Evidence for local eosinophil differentiation within allergic nasal mucosa: inhibition with soluble IL-5 receptor
L Cameron1, P Christodoulopoulos, F Lavigne
1Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Abstract:
Eosinophil differentiation occurs within the bone marrow in response to eosinopoietic cytokines, particularly IL-5. Recently, however, eosinophil precursors (CD34/IL-5Ralpha+ 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-5Ralpha (sIL-5Ralpha), shown to antagonize IL-5 function. Simultaneous immunocytochemistry and in situ hybridization demonstrated that there were fewer cells coexpressing CD34 immunoreactivity and IL-5Ralpha 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-5Ralpha. 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-5Ralpha.
Insights
Eosinophil precursors in allergic nasal tissue can differentiate locally, driven by interleukin-5 (IL-5). This local differentiation is inhibited by soluble IL-5 receptor alpha (sIL-5Ralpha), suggesting in vivo regulation.
Area of Science:
- Immunology
- Respiratory Medicine
Background:
- Eosinophil differentiation typically occurs in bone marrow, regulated by cytokines like IL-5.
- Recent findings suggest potential in situ eosinophil differentiation in asthmatic lungs.
- Eosinophil precursors and IL-5 mRNA have been found in asthmatic lungs.
Purpose of the Study:
- To investigate the presence of eosinophil precursors in allergic nasal mucosa.
- To determine if these precursors undergo local differentiation ex vivo.
- To explore the role of IL-5 and its antagonist, sIL-5Ralpha, in this process.
Main Methods:
- Human nasal mucosa from allergic rhinitis patients was cultured ex vivo.
- Cultures were stimulated with allergen, recombinant human IL-5 (rhIL-5), or allergen + soluble IL-5Ralpha (sIL-5Ralpha).
- Immunocytochemistry, in situ hybridization, and colocalization analysis were used to identify cell types and gene expression.
Main Results:
- Allergen or rhIL-5 stimulation decreased CD34/IL-5Ralpha mRNA co-expressing cells but increased major basic protein (MBP)-positive eosinophils.
- IL-5 mRNA+ cells increased in allergen-stimulated tissue.
- These effects were blocked by sIL-5Ralpha, which also revealed IL-5 mRNA expression in T cells and eosinophils.
Conclusions:
- Eosinophil precursors can differentiate locally within allergic nasal mucosa.
- This local differentiation is IL-5 dependent.
- Endogenous sIL-5Ralpha may regulate this in vivo process.