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on Human Eosinophils: I. Loss of Membrane IL-5 Receptor on Airway Eosinophils and Increased Soluble IL-5 Receptor in the Airway After Allergen Challenge1
* Allergy and Immunology and
Pulmonary and Critical Care Sections of Department of Medicine, and Departments of
Biomolecular Chemistry and
Pediatrics, University of Wisconsin, Madison, WI 53792; and
¶ Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905
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-5R
on bronchoalveolar lavage (BAL) eosinophils; 2) the
responsiveness of these cells to exogenous IL-5; and 3) the presence of
soluble (s)IL-5R 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-5R on airway eosinophils compared with circulating cells.
Furthermore, sIL-5R concentrations were elevated in BAL fluid, but
steady state levels of sIL-5R 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-5R on BAL eosinophils may regulate IL-5-mediated
eosinophil functions. Together, the loss of mIL-5R, the presence of
sIL-5R, 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.
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