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

AbstractBACKGROUND:
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.
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.
AuthorsJ A Denburg, R Sehmi, J Upham, L Wood, G Gauvreau, P O'Byrne
JournalInternational archives of allergy and immunology (Int Arch Allergy Immunol) 1999 Feb-Apr Vol. 118 Issue 2-4 Pg. 101-3 ISSN: 1018-2438 [Print] Switzerland
PMID10224351 (Publication Type: Journal Article)
Chemical References
  • Interleukin-5
  • Receptors, Interleukin
  • Receptors, Interleukin-5
Topics
  • Asthma (immunology, pathology)
  • Bone Marrow Cells (immunology, pathology)
  • Cell Differentiation (immunology)
  • Eosinophils (immunology, pathology)
  • Humans
  • Interleukin-5 (biosynthesis, immunology)
  • Receptors, Interleukin (biosynthesis, immunology)
  • Receptors, Interleukin-5

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