Invited Symposium: Novel Cellular and Molecular Mechanisms in Allergic Inflammation
Sehmi, R. (Dept of Medicine, Division of Clinical Immunology & Allergy, McMaster University, Canada)
Upham, J. (Dept of Medicine, Division of Respirology, McMaster University, Canada)
Lundahl, J. (Dept of Medicine, Division of Clinical Immunology & Allergy, McMaster University, Canada)
Wood, L. (Dept of Medicine, Division of Respirology, McMaster University, Canada)
Gauvreau, G. (Dept of Medicine, Division of Respirology, McMaster University, Canada)
O'Byrne, P. (Dept of Medicine, Division of Respirology, McMaster University, Canada)
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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|Denburg, JA; Sehmi, R.; Upham, J.; Lundahl, J.; Wood, L.; Gauvreau, G.; O'Byrne, P.; (1998). Regulation of IL-5 and IL-5 Receptor Expression in the Bone Marrow of Allergic Asthmatics. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/denburg/denburg0270/index.html|
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