Regulation of IL–5 and IL–5 Receptor Expression in the Bone Marrow of Allergic Asthmatics

Abstract

Background: Following consistent demonstrations of the clinical relevance of fluctuations in eosinophil–basophil (Eo–B) progenitors in the blood of patients with a variety of allergic airway disorders, we have turned our attention recently to hemopoietic events occurring in the bone marrow of allergic asthmatic subjects, utilizing a model of airway allergen challenge. Methods: Flow–cytometric analyses of CD34/45+ progenitors for coexpression of surface α–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 before and after in vivo allergen challenge. Results: An early, specific upregulation of IL–5R α expression on CD34/45 progenitors was observed after allergen challenge, concomitant with the development of the late–phase asthmatic response. Protein and mRNA for both GM–CSF and IL–5 were expressed in a time–dependent manner ex vivo, in developing (β 7–integrin–positive), colony–derived Eo–B after allergen challenge in vivo. Both retinoic acid and corticosteroids were able to downregulate IL–3– and IL–5–induced expression of IL–5R on cord–blood–derived as well as HL–60 cloned Eo–B progenitors. Conclusion: These studies indicate the critical involvement of IL–5 and IL–5R in the induction of Eo–B differentiation and eosinophilic airway inflammation in allergic asthmatics, and point to these events as potential targets for long–term therapy of atopic disease.