Regulation of IL-5 and IL-5 receptor expression in the bone marrow of allergic asthmatics

Background: Following consistent demonstrations of the clinical relevance o f fluctuations in eosinophil-basophil (Eo-B) progenitors in the blood of pa tients with a variety of allergic airway disorders, we have turned our atte ntion recently to hemopoietic events occurring in the bone marrow of allerg ic asthmatic subjects, utilizing a model of airway allergen challenge. Meth ods: Flowcytometric analyses of CD34/45+ progenitors for coexpression of su rface alpha-receptor subunits for IL-3, IL-5 and GM-CSF, as well as in situ hybridization and in situ PCR methodologies to detect mRNA for IL-5 and GM -CSF in developing Eo-B in colony and liquid culture assays were employed b efore and after in vivo allergen challenge, Results: An early, specific upr egulation of IL-5R alpha expression on CD34/45 progenitors was observed aft er allergen challenge, concomitant with the development of the late-phase a sthmatic response. Protein and mRNA for both GM-CSF and IL-5 were expressed in a time-dependent manner ex vivo, in developing (beta 7-integrin-positiv e), colony-derived Eo-B after allergen challenge in vivo, Both retinoic aci d and corticosteroids were able to downregulate IL-3- and IL-5-induced expr ession of IL-5R on cord-blood-derived as well as HL-60 cloned Eo-B progenit ors. Conclusion: These studies indicate the critical involvement of IL-5 an d IL-5R in the induction of Eo-B differentiation and eosinophilic airway in flammation in allergic asthmatics, and point to these events as potential t argets for long-term therapy of atopic disease.