Decreased expression of membrane IL-5 receptor α on human eosinophils: I. Loss of membrane IL-5 receptor α on airway eosinophils and increased soluble IL-5 receptor α in the airway after allergen challenge

Lin Ying Liu, Julie B. Sedgwick, Mary Ellen Bates, Rose F. Vrtis, James E. Gern, Hirohita Kita, Nizar N. Jarjour, William W. Busse, Elizabeth A.B. Kelly

Research output: Contribution to journalArticle

148 Scopus citations

Abstract

IL-5 is a key cytokine for eosinophil maturation, recruitment, activation, and possibly the development of inflammation in asthma. High concentrations of IL-5 are present in the airway after Ag challenge, but the responsiveness of airway eosinophils to IL-5 is not well characterized. The objectives of this study were to establish, following airway Ag challenge: 1) the expression of membrane (m)IL-5Rα on bronchoalveolar lavage (BAL) eosinophils; 2) the responsiveness of these cells to exogenous IL-5; and 3) the presence of soluble (s)IL-5Rα in BAL fluid. To accomplish these goals, blood and BAL eosinophils were obtained from atopic subjects 48 h after segmental bronchoprovocation with Ag. There was a striking reduction in mIL-5Rα on airway eosinophils compared with circulating cells. Furthermore, sIL-5Rα concentrations were elevated in BAL fluid, but steady state levels of sIL-5Rα mRNA were not increased in BAL compared with blood eosinophils. Finally, BAL eosinophils were refractory to IL-5 for ex vivo degranulation, suggesting that the reduction in mIL-5Rα on BAL eosinophils may regulate IL-5-mediated eosinophil functions. Together, the loss of mIL-5Rα, the presence of sIL-5Rα, and the blunted functional response (degranulation) of eosinophils to IL-5 suggest that when eosinophils are recruited to the airway, regulation of their functions becomes IL-5 independent. These observations provide a potential explanation for the inability of anti-IL-5 therapy to suppress airway hyperresponsiveness to inhaled Ag, despite a reduction in eosinophil recruitment.

Original languageEnglish (US)
Pages (from-to)6452-6458
Number of pages7
JournalJournal of Immunology
Volume169
Issue number11
DOIs
StatePublished - Dec 1 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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