Decreased expression of membrane IL-5 receptor alpha on human eosinophils: I. Loss of membrane IL-5 receptor alpha on airway eosinophils and increased soluble IL-5 receptor alpha in the airway after allergen challenge.
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-5Ralpha on bronchoalveolar lavage (BAL) eosinophils; 2) the responsiveness of these cells to exogenous IL-5; and 3) the presence of soluble (s)IL-5Ralpha 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-5Ralpha on airway eosinophils compared with circulating cells. Furthermore, sIL-5Ralpha concentrations were elevated in BAL fluid, but steady state levels of sIL-5Ralpha 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-5Ralpha on BAL eosinophils may regulate IL-5-mediated eosinophil functions. Together, the loss of mIL-5Ralpha, the presence of sIL-5Ralpha, 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.
Liu
Lin Ying
LY
Allergy and Immunology, Department of Medicine, University of Wisconsin, Madison 53792, USA.
Sedgwick
Julie B
JB
Bates
Mary Ellen
ME
Vrtis
Rose F
RF
Gern
James E
JE
Kita
Hirohita
H
Jarjour
Nizar N
NN
Busse
William W
WW
Kelly
Elizabeth A B
EA
D000328:Adult; D000485:Allergens / Q000008:administration & dosage; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology* / Q000276:immunology*; D015550:Cell Degranulation / Q000187:drug effects; D002462:Cell Membrane / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000276:immunology / Q000473:pathology; D066298:In Vitro Techniques; D015848:Interleukin-5 / Q000378:metabolism / Q000494:pharmacology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics* / Q000378:metabolism*; D053649:Receptors, Interleukin-5; D011994:Recombinant Proteins; D012995:Solubility
D000485:Allergens; D015848:Interleukin-5; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor