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Differential expression of the interleukin 5 receptor α isoforms in blood and tissue eosinophils of nasal polyp patients
Author(s) -
Gevaert P.,
Hellman C.,
Lundblad L.,
Lundahl J.,
Holtappels G.,
Van Cauwenberge P.,
Tavernier J.,
Bachert C.
Publication year - 2009
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2008.01885.x
Subject(s) - eosinophil , interleukin 5 , gene isoform , peripheral blood mononuclear cell , messenger rna , immunology , interleukin , nasal polyps , eosinophil cationic protein , gene expression , whole blood , endocrinology , biology , medicine , microbiology and biotechnology , in vitro , cytokine , asthma , gene , biochemistry
Background: Given the key role of interleukin‐5 (IL‐5) in eosinophil function, we investigated the regulated expression of the membrane‐anchored (TM‐IL‐5Rα) isoform, or a secreted (SOL IL‐5Rα) isoform, on both protein and transcript level in vitro and in vivo . Methods: A real‐time PCR, FACS and ELISA were established to determine IL‐5Rα 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‐5Rα and TM‐IL‐5Rα mRNA and protein levels in comparison with CD‐69 expression. Results: SOL‐IL‐5Rα and TM‐IL‐5Rα mRNA and protein expression was significantly increased in NP vs controls. In polyp tissue, SOL‐IL‐5Rα expression correlated to disease severity and eosinophils counts, whereas TM‐IL‐5Rα levels were inversely correlated to eosinophils counts and SOL‐IL‐5Rα expression. FACS analysis revealed increased CD‐69 and decreased TM‐IL‐5Rα 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‐5Rα after 2 and 24 h. Conclusion: The expression of SOL‐IL‐5Rα and TM‐IL‐5Rα 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‐5Rα isoforms. Since, TM‐IL‐5Rα is down‐regulated and SOL‐IL‐5Rα (antagonistic) is upregulated in NP tissue, our findings are important to understand the clinical trials with anti‐IL‐5 in humans.