Differential expression of the interleukin 5 receptor alpha isoforms in blood and tissue eosinophils of nasal polyp patients
- Author
- Philippe Gevaert (UGent) , C. Hellman, L. Lundblad, J. Lundahl, Gabriële Holtappels (UGent) , Paul Van Cauwenberge (UGent) , Jan Tavernier (UGent) and Claus Bachert (UGent)
- Organization
- Abstract
- Given the key role of interleukin-5 (IL-5) in eosinophil function, we investigated the regulated expression of the membrane-anchored (TM-IL-5R alpha) isoform, or a secreted (SOL IL-5R alpha) isoform, on both protein and transcript level in vitro and in vivo. A real-time PCR, FACS and ELISA were established to determine IL-5R alpha isoform expression in peripheral blood and nasal tissue from control subjects and nasal polyp (NP) patients with or without asthma. Human peripheral blood eosinophils were incubated with IL-5 and were analyzed for SOL-IL-5R alpha and TM-IL-5R alpha mRNA and protein levels in comparison with CD-69 expression. SOL-IL-5R alpha and TM-IL-5R alpha mRNA and protein expression was significantly increased in NP vs controls. In polyp tissue, SOL-IL-5R alpha expression correlated to disease severity and eosinophils counts, whereas TM-IL-5R alpha levels were inversely correlated to eosinophils counts and SOL-IL-5R alpha expression. FACS analysis revealed increased CD-69 and decreased TM-IL-5R alpha expression in NP tissue eosinophils vs blood eosinophils. Incubation of blood eosinophils with IL-5 caused up-regulation of CD-69 and down-regulation of TM-IL-5R alpha after 2 and 24 h. The expression of SOL-IL-5R alpha and TM-IL-5R alpha differs according to the eosinophil activation state and localization in the body (blood vs tissue) and may therefore be involved in the fine-tuning of the eosinophil homeostasis. Exposure of eosinophils to IL-5 reduces their responsiveness to IL-5 by regulated expression of the IL-5R alpha isoforms. Since, TM-IL-5R alpha is down-regulated and SOL-IL-5R alpha (antagonistic) is upregulated in NP tissue, our findings are important to understand the clinical trials with anti-IL-5 in humans.
- Keywords
- rhinosinusitis, KeyWords Plus: SOLUBLE IL-5 RECEPTOR, DECREASED EXPRESSION, ALLERGEN CHALLENGE, GM-CSF, INHIBITION, SUBUNIT, INFLAMMATION, CYTOKINES, AIRWAY, CHAIN, nasal polyps, eosinophils, IL-5 receptor alpha
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-664840
- MLA
- Gevaert, Philippe, et al. “Differential Expression of the Interleukin 5 Receptor Alpha Isoforms in Blood and Tissue Eosinophils of Nasal Polyp Patients.” ALLERGY, vol. 64, no. 5, WILEY-BLACKWELL PUBLISHING, INC, 2009, pp. 725–32, doi:10.1111/j.1398-9995.2008.01885.x.
- APA
- Gevaert, P., Hellman, C., Lundblad, L., Lundahl, J., Holtappels, G., Van Cauwenberge, P., … Bachert, C. (2009). Differential expression of the interleukin 5 receptor alpha isoforms in blood and tissue eosinophils of nasal polyp patients. ALLERGY, 64(5), 725–732. https://doi.org/10.1111/j.1398-9995.2008.01885.x
- Chicago author-date
- Gevaert, Philippe, C. Hellman, L. Lundblad, J. Lundahl, Gabriële Holtappels, Paul Van Cauwenberge, Jan Tavernier, and Claus Bachert. 2009. “Differential Expression of the Interleukin 5 Receptor Alpha Isoforms in Blood and Tissue Eosinophils of Nasal Polyp Patients.” ALLERGY 64 (5): 725–32. https://doi.org/10.1111/j.1398-9995.2008.01885.x.
- Chicago author-date (all authors)
- Gevaert, Philippe, C. Hellman, L. Lundblad, J. Lundahl, Gabriële Holtappels, Paul Van Cauwenberge, Jan Tavernier, and Claus Bachert. 2009. “Differential Expression of the Interleukin 5 Receptor Alpha Isoforms in Blood and Tissue Eosinophils of Nasal Polyp Patients.” ALLERGY 64 (5): 725–732. doi:10.1111/j.1398-9995.2008.01885.x.
- Vancouver
- 1.Gevaert P, Hellman C, Lundblad L, Lundahl J, Holtappels G, Van Cauwenberge P, et al. Differential expression of the interleukin 5 receptor alpha isoforms in blood and tissue eosinophils of nasal polyp patients. ALLERGY. 2009;64(5):725–32.
- IEEE
- [1]P. Gevaert et al., “Differential expression of the interleukin 5 receptor alpha isoforms in blood and tissue eosinophils of nasal polyp patients,” ALLERGY, vol. 64, no. 5, pp. 725–732, 2009.
@article{664840, abstract = {{Given the key role of interleukin-5 (IL-5) in eosinophil function, we investigated the regulated expression of the membrane-anchored (TM-IL-5R alpha) isoform, or a secreted (SOL IL-5R alpha) isoform, on both protein and transcript level in vitro and in vivo. A real-time PCR, FACS and ELISA were established to determine IL-5R alpha isoform expression in peripheral blood and nasal tissue from control subjects and nasal polyp (NP) patients with or without asthma. Human peripheral blood eosinophils were incubated with IL-5 and were analyzed for SOL-IL-5R alpha and TM-IL-5R alpha mRNA and protein levels in comparison with CD-69 expression. SOL-IL-5R alpha and TM-IL-5R alpha mRNA and protein expression was significantly increased in NP vs controls. In polyp tissue, SOL-IL-5R alpha expression correlated to disease severity and eosinophils counts, whereas TM-IL-5R alpha levels were inversely correlated to eosinophils counts and SOL-IL-5R alpha expression. FACS analysis revealed increased CD-69 and decreased TM-IL-5R alpha expression in NP tissue eosinophils vs blood eosinophils. Incubation of blood eosinophils with IL-5 caused up-regulation of CD-69 and down-regulation of TM-IL-5R alpha after 2 and 24 h. The expression of SOL-IL-5R alpha and TM-IL-5R alpha differs according to the eosinophil activation state and localization in the body (blood vs tissue) and may therefore be involved in the fine-tuning of the eosinophil homeostasis. Exposure of eosinophils to IL-5 reduces their responsiveness to IL-5 by regulated expression of the IL-5R alpha isoforms. Since, TM-IL-5R alpha is down-regulated and SOL-IL-5R alpha (antagonistic) is upregulated in NP tissue, our findings are important to understand the clinical trials with anti-IL-5 in humans.}}, author = {{Gevaert, Philippe and Hellman, C. and Lundblad, L. and Lundahl, J. and Holtappels, Gabriële and Van Cauwenberge, Paul and Tavernier, Jan and Bachert, Claus}}, issn = {{0105-4538}}, journal = {{ALLERGY}}, keywords = {{rhinosinusitis,KeyWords Plus: SOLUBLE IL-5 RECEPTOR,DECREASED EXPRESSION,ALLERGEN CHALLENGE,GM-CSF,INHIBITION,SUBUNIT,INFLAMMATION,CYTOKINES,AIRWAY,CHAIN,nasal polyps,eosinophils,IL-5 receptor alpha}}, language = {{eng}}, number = {{5}}, pages = {{725--732}}, publisher = {{WILEY-BLACKWELL PUBLISHING, INC}}, title = {{Differential expression of the interleukin 5 receptor alpha isoforms in blood and tissue eosinophils of nasal polyp patients}}, url = {{http://doi.org/10.1111/j.1398-9995.2008.01885.x}}, volume = {{64}}, year = {{2009}}, }
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