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. CONCLUSION: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.

journal_name

Allergy

journal_title

Allergy

authors

Gevaert P,Hellman C,Lundblad L,Lundahl J,Holtappels G,van Cauwenberge P,Tavernier J,Bachert C

doi

10.1111/j.1398-9995.2008.01885.x

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

725-32

issue

5

eissn

0105-4538

issn

1398-9995

pii

ALL1885

journal_volume

64

pub_type

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