title: Differential expression of the interleukin 5 receptor alpha isoforms in blood and tissue eosinophils of nasal polyp patients.
abstract: BACKGROUND
  Given the key role of interleukin-5 (IL-5) in eosinophil function, we investigated the regulated expression of the membrane-anchored (TM-IL-5Ralpha) isoform, or a secreted (SOL IL-5Ralpha) 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-5Ralpha 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-5Ralpha and TM-IL-5Ralpha mRNA and protein levels in comparison with CD-69 expression.
  
  
  RESULTS
  SOL-IL-5Ralpha and TM-IL-5Ralpha mRNA and protein expression was significantly increased in NP vs controls. In polyp tissue, SOL-IL-5Ralpha expression correlated to disease severity and eosinophils counts, whereas TM-IL-5Ralpha levels were inversely correlated to eosinophils counts and SOL-IL-5Ralpha expression. FACS analysis revealed increased CD-69 and decreased TM-IL-5Ralpha 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-5Ralpha after 2 and 24 h.
  
  
  CONCLUSIONS
  The expression of SOL-IL-5Ralpha and TM-IL-5Ralpha 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-5Ralpha isoforms. Since, TM-IL-5Ralpha is down-regulated and SOL-IL-5Ralpha (antagonistic) is upregulated in NP tissue, our findings are important to understand the clinical trials with anti-IL-5 in humans.
authors.affiliation: Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University, Ghent, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Gevaert
authors.forename: C
authors.initials: C
authors.lastname: Hellman
authors.forename: L
authors.initials: L
authors.lastname: Lundblad
authors.forename: J
authors.initials: J
authors.lastname: Lundahl
authors.forename: G
authors.initials: G
authors.lastname: Holtappels
authors.forename: P
authors.initials: P
authors.lastname: van Cauwenberge
authors.forename: J
authors.initials: J
authors.lastname: Tavernier
authors.forename: C
authors.initials: C
authors.lastname: Bachert
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology; D053666:Interleukin-5 Receptor alpha Subunit / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000276:immunology* / Q000378:metabolism; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015848:Interleukin-5; D053666:Interleukin-5 Receptor alpha Subunit; D037181:Lectins, C-Type; D020033:Protein Isoforms; D000099192:CD69 Antigens