Regulation of IL-5 and IL-5 receptor expression in the bone marrow of allergic asthmatics.
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 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 before and after in vivo allergen challenge.


RESULTS
An early, specific upregulation of IL-5R alpha 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 (beta 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.


CONCLUSIONS
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.
Denburg
J A
JA
Asthma Research Group, Division of Clinical Immunology and Allergy, Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Sehmi
R
R
Upham
J
J
Wood
L
L
Gauvreau
G
G
O'Byrne
P
P
D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D006801:Humans; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology*; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000276:immunology*; D053649:Receptors, Interleukin-5
D015848:Interleukin-5; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5