Abstract

Introduction

Progenitors in airways inflammation

Allergen challenge studies in asthma

Topical corticosteroid therapy

Novel therapies

Discussion
Board

Following on consistent demonstrations of the clinical relevance of fluctuations in eosinophil-basophil (Eo-B) progenitors in the blood of patients with a variety of allergic airways disorders, we have turned our attention recently to hemopoietic events taking place in the bone marrow of allergic asthmatic subjects, utilising a model of airway allergen challenge. Flow cytometric analyses of CD34/45+ bone marrow progenitors for co-expression of surface alpha-receptor subunits for IL-3, IL-5 and GM-CSF, as well as in situ hybridisation 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 in several studies before and after in vivo allergen challenge. An early, specific up-regulation of IL-5R-alpha expression on CD34/45 progenitors in the marrow was observed after allergen, co-temporaneous 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 fashion ex vivo, in developing (beta 7-integrin-positive) colony-derived Eo-B after allergen challenge in vivo. In vitro studies revealed that retinoic acid was able to down-regulate expression of IL-5R-alpha on cord blood-derived, as well as HL-60 cloned, Eo-B progenitors. These studies indicate the critical involvement of IL-5 and IL-5R in the induction of Eo-B differentiation and eosinophilic airways inflammation in allergic asthmatics, and point to these events as potential targets for long-term therapy of atopic disease.

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Presentation Number SAdenburg0270
Keywords: asthma, hemopoiesis, Interleukin-5, cytokines, allergy