Invited Symposium: Novel Cellular and Molecular Mechanisms in Allergic Inflammation
Robinson, D (Allergy and Clinical Immunology, Imperial College School of Medicine at NHLI, London, UK)
Interleukin 5 plays a critical role in the expansion, differentiation and activation of the eosinophilic (and basophilic) cell type. In line with such specific role, expression of the interleukin 5 receptor alpha-subunit is restricted to eosinophils and basophils in man. In the mouse, B1-cell-specific expression is also observed. Expression levels in eosinophilic cell types appear to be determined by a combination of (i) the use of a composite promoter, and (ii) controlled alternative splicing. We have studied the latter control level in cell lines and in CD34+ cord blood progenitor cells. Alternative splicing yields transcripts from the hIL-5Ralpha gene which can either encode a signalling, membrane-anchored (IL-5Ralpha-TM) or a secreted variant with receptor antagonist activity (IL-5Ralpha-SOL). In a murine, promyelocytic FDC-P1cell line, stably transfected with a human IL-5Ralpha minigene construct, IL-5 itself, but not IL-3 or GM-CSF, can stimulate a reversible switch towards expression of the membrane-associated isoform, implying an IL-5/IL-5Ralpha-specific signalling event. Moreover, an IL-5-associated switch from predominantly soluble isoform to IL-5Ralpha-TM mRNA expression, with concomitant increase in IL-5 responsiveness, was shown during differentiation of human cord blood CD34+ cells to the eosinophilic lineage. Our results indicate ligand-dependent control of receptor expression, which may have general importance in understanding cytokine receptor regulation, and suggest a potential therapeutic intervention target.
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|Tavernier, J; Robinson, D; (1998). Interleukin 5 Receptor Biology. 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/tavernier0544/index.html|
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