Decreased expression of membrane IL-5 receptor α on human eosinophils: II. IL-5 down-modulates its receptor via a proteinase-mediated process

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

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Abstract

In the accompanying study, we demonstrated that following Ag challenge, membrane (m)IL-5Rα expression is attenuated on bronchoalveolar lavage eosinophils, soluble (s)IL-5Rα is detectable in BAL fluid in the absence of increased steady state levels of sIL-5Rα mRNA, and BAL eosinophils become refractory to IL-5 for ex vivo degranulation. We hypothesized that IL-5 regulates its receptor through proteolytic release of mIL-5Rα, which in turn contributes to the presence of sIL-5Rα. Purified human peripheral blood eosinophils were incubated with IL-5 under various conditions and in the presence of different pharmacological agents. A dose-dependent decrease in mIL-5Rα was accompanied by an increase in sIL-5Rα in the supernatant. IL-5 had no ligand-specific effect on mIL-5Rα or sIL-5Rα mRNA levels. The matrix metalloproteinase-specific inhibitors BB-94 and GM6001 and tissue inhibitor of metalloproteinase-3 partially inhibited IL-5-mediated loss of mIL-5Rα, suggesting that sIL-5Rα may be produced by proteolytic cleavage of mIL-5Rα. IL-5 transiently reduced surface expression of β-chain, but had no effect on the expression of GM-CSFRα. Pretreatment of eosinophils with a dose of IL-5 that down-modulated mIL-5Rα rendered these cells unable to degranulate in response to further IL-5 stimulation, but they were fully responsive to GM-CSF. These findings suggest that IL-5-activated eosinophils may lose mIL-5Rα and release sIL-5Rα in vivo, which may limit IL-5-dependent inflammatory events in diseases such as asthma.

Original languageEnglish (US)
Pages (from-to)6459-6466
Number of pages8
JournalJournal of Immunology
Volume169
Issue number11
StatePublished - Dec 1 2002

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Interleukin-5 Receptors
Interleukin-5
Eosinophils
Peptide Hydrolases
Membranes
Dimercaprol
Tissue Inhibitor of Metalloproteinase-3
Messenger RNA
Matrix Metalloproteinase Inhibitors
Bronchoalveolar Lavage
Granulocyte-Macrophage Colony-Stimulating Factor

ASJC Scopus subject areas

  • Immunology

Cite this

Liu, L. Y., Sedgwick, J. B., Bates, M. E., Vrtis, R. F., Gern, J. E., Kita, H., ... Kelly, E. A. B. (2002). Decreased expression of membrane IL-5 receptor α on human eosinophils: II. IL-5 down-modulates its receptor via a proteinase-mediated process. Journal of Immunology, 169(11), 6459-6466.

Decreased expression of membrane IL-5 receptor α on human eosinophils : II. IL-5 down-modulates its receptor via a proteinase-mediated process. / Liu, Lin Ying; Sedgwick, Julie B.; Bates, Mary Ellen; Vrtis, Rose F.; Gern, James E.; Kita, Hirohito; Jarjour, Nizar N.; Busse, William W.; Kelly, Elizabeth A B.

In: Journal of Immunology, Vol. 169, No. 11, 01.12.2002, p. 6459-6466.

Research output: Contribution to journalArticle

Liu, LY, Sedgwick, JB, Bates, ME, Vrtis, RF, Gern, JE, Kita, H, Jarjour, NN, Busse, WW & Kelly, EAB 2002, 'Decreased expression of membrane IL-5 receptor α on human eosinophils: II. IL-5 down-modulates its receptor via a proteinase-mediated process', Journal of Immunology, vol. 169, no. 11, pp. 6459-6466.
Liu, Lin Ying ; Sedgwick, Julie B. ; Bates, Mary Ellen ; Vrtis, Rose F. ; Gern, James E. ; Kita, Hirohito ; Jarjour, Nizar N. ; Busse, William W. ; Kelly, Elizabeth A B. / Decreased expression of membrane IL-5 receptor α on human eosinophils : II. IL-5 down-modulates its receptor via a proteinase-mediated process. In: Journal of Immunology. 2002 ; Vol. 169, No. 11. pp. 6459-6466.
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abstract = "In the accompanying study, we demonstrated that following Ag challenge, membrane (m)IL-5Rα expression is attenuated on bronchoalveolar lavage eosinophils, soluble (s)IL-5Rα is detectable in BAL fluid in the absence of increased steady state levels of sIL-5Rα mRNA, and BAL eosinophils become refractory to IL-5 for ex vivo degranulation. We hypothesized that IL-5 regulates its receptor through proteolytic release of mIL-5Rα, which in turn contributes to the presence of sIL-5Rα. Purified human peripheral blood eosinophils were incubated with IL-5 under various conditions and in the presence of different pharmacological agents. A dose-dependent decrease in mIL-5Rα was accompanied by an increase in sIL-5Rα in the supernatant. IL-5 had no ligand-specific effect on mIL-5Rα or sIL-5Rα mRNA levels. The matrix metalloproteinase-specific inhibitors BB-94 and GM6001 and tissue inhibitor of metalloproteinase-3 partially inhibited IL-5-mediated loss of mIL-5Rα, suggesting that sIL-5Rα may be produced by proteolytic cleavage of mIL-5Rα. IL-5 transiently reduced surface expression of β-chain, but had no effect on the expression of GM-CSFRα. Pretreatment of eosinophils with a dose of IL-5 that down-modulated mIL-5Rα rendered these cells unable to degranulate in response to further IL-5 stimulation, but they were fully responsive to GM-CSF. These findings suggest that IL-5-activated eosinophils may lose mIL-5Rα and release sIL-5Rα in vivo, which may limit IL-5-dependent inflammatory events in diseases such as asthma.",
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AU - Bates, Mary Ellen

AU - Vrtis, Rose F.

AU - Gern, James E.

AU - Kita, Hirohito

AU - Jarjour, Nizar N.

AU - Busse, William W.

AU - Kelly, Elizabeth A B

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N2 - In the accompanying study, we demonstrated that following Ag challenge, membrane (m)IL-5Rα expression is attenuated on bronchoalveolar lavage eosinophils, soluble (s)IL-5Rα is detectable in BAL fluid in the absence of increased steady state levels of sIL-5Rα mRNA, and BAL eosinophils become refractory to IL-5 for ex vivo degranulation. We hypothesized that IL-5 regulates its receptor through proteolytic release of mIL-5Rα, which in turn contributes to the presence of sIL-5Rα. Purified human peripheral blood eosinophils were incubated with IL-5 under various conditions and in the presence of different pharmacological agents. A dose-dependent decrease in mIL-5Rα was accompanied by an increase in sIL-5Rα in the supernatant. IL-5 had no ligand-specific effect on mIL-5Rα or sIL-5Rα mRNA levels. The matrix metalloproteinase-specific inhibitors BB-94 and GM6001 and tissue inhibitor of metalloproteinase-3 partially inhibited IL-5-mediated loss of mIL-5Rα, suggesting that sIL-5Rα may be produced by proteolytic cleavage of mIL-5Rα. IL-5 transiently reduced surface expression of β-chain, but had no effect on the expression of GM-CSFRα. Pretreatment of eosinophils with a dose of IL-5 that down-modulated mIL-5Rα rendered these cells unable to degranulate in response to further IL-5 stimulation, but they were fully responsive to GM-CSF. These findings suggest that IL-5-activated eosinophils may lose mIL-5Rα and release sIL-5Rα in vivo, which may limit IL-5-dependent inflammatory events in diseases such as asthma.

AB - In the accompanying study, we demonstrated that following Ag challenge, membrane (m)IL-5Rα expression is attenuated on bronchoalveolar lavage eosinophils, soluble (s)IL-5Rα is detectable in BAL fluid in the absence of increased steady state levels of sIL-5Rα mRNA, and BAL eosinophils become refractory to IL-5 for ex vivo degranulation. We hypothesized that IL-5 regulates its receptor through proteolytic release of mIL-5Rα, which in turn contributes to the presence of sIL-5Rα. Purified human peripheral blood eosinophils were incubated with IL-5 under various conditions and in the presence of different pharmacological agents. A dose-dependent decrease in mIL-5Rα was accompanied by an increase in sIL-5Rα in the supernatant. IL-5 had no ligand-specific effect on mIL-5Rα or sIL-5Rα mRNA levels. The matrix metalloproteinase-specific inhibitors BB-94 and GM6001 and tissue inhibitor of metalloproteinase-3 partially inhibited IL-5-mediated loss of mIL-5Rα, suggesting that sIL-5Rα may be produced by proteolytic cleavage of mIL-5Rα. IL-5 transiently reduced surface expression of β-chain, but had no effect on the expression of GM-CSFRα. Pretreatment of eosinophils with a dose of IL-5 that down-modulated mIL-5Rα rendered these cells unable to degranulate in response to further IL-5 stimulation, but they were fully responsive to GM-CSF. These findings suggest that IL-5-activated eosinophils may lose mIL-5Rα and release sIL-5Rα in vivo, which may limit IL-5-dependent inflammatory events in diseases such as asthma.

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