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Blood, 15 September 2000, Vol. 96, No. 6, pp. 2163-2171

IMMUNOBIOLOGY

Interleukin-9 enhances interleukin-5 receptor expression, differentiation, and survival of human eosinophils

Abdelilah Soussi Gounni, Bernard Gregory, Esra Nutku, Fadi Aris, Koussih Latifa, Eleanor Minshall, Janet North, Jan Tavernier, Roy Levit, Nick Nicolaides, Douglas Robinson, and Qutayba Hamid

From Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada; the Department of Allergy and Clinical Immunology, Imperial College School of Medicine, National Heart and Lung Institute, London, England; the Department of Medical Protein Chemistry, Flanders InterUniversity Institute for Biotechnology, Ghent, Belgium; and Magainin Pharmaceuticals, Plymouth Meeting, PA.

Interleukin-9 (IL-9) has been implicated in the pathogenesis of allergic disorders. To examine the interaction between IL-9 and eosinophils, we evaluated mature peripheral blood eosinophils for their expression of the specific alpha -subunit of the IL-9 receptor (IL-9R-alpha ). The expression of IL-9R-alpha by human eosinophils was detected at the messenger RNA (mRNA) and protein levels by reverse transcriptase-polymerase chain reaction (RT-PCR), flow cytometry, and immunocytochemical analysis, respectively. Functional analyses demonstrated that recombinant human (rh)IL-9 inhibited in vitro peripheral blood human eosinophil apoptosis in a concentration-dependent manner. We then examined the role of IL-9 in eosinophil differentiation using the human cord blood CD34+ cells and human promyelocytic leukemia cells (HL-60). The addition of IL-9 to CD34+ cells cultured in IL-3 and IL-5 enhanced eosinophil development, and IL-9 alone induced the expression of IL-5R-alpha . IL-9 also up-regulated the IL-5R-alpha chain cell surface expression during terminal eosinophil differentiation of the HL-60 cell line. Our findings suggest that IL-9 may potentiate in vivo eosinophil function by increasing their survival and IL-5-mediated differentiation and maturation. Taken together, these results suggest a mechanism by which IL-9 potentiates airway and tissue eosinophilia.

© 2000 by The American Society of Hematology.
 

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