Airway allergen exposure stimulates bone marrow eosinophilia partly via IL-9 |
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| Authors: | Brigita Sitkauskiene Madeleine R?dinger Apostolos Bossios Anna-Karin Johansson Raimundas Sakalauskas Jan L?tvall |
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| Affiliation: | 1.The Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Institute of Internal Medicine, Göteborg University, Guldhedsgatan 10A, 413 46 Gothenburg, Sweden;2.Department of Pulmonology and Immunology, Kaunas University of Medicine, Eiveniu 2, 50009 Kaunas, Lithuania;3.Lab of Pulmonology, Institute for Biomedical Research, Kaunas University of Medicine, Eiveniu 4, 50009 Kaunas, Lithuania |
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| Abstract: | BackgroundInterleukin (IL)-9 is a Th2-derived cytokine with pleiotropic biological effects, which recently has been proposed as a candidate gene for asthma and allergy. We aimed to evaluate the therapeutic effect of a neutralizing anti-IL-9 antibody in a mouse model of airway eosinophilic inflammation and compared any such effect with anti-IL-5 treatment.MethodsOVA-sensitized Balb/c mice were intraperitoneally pretreated with a single dose (100 μg) of an anti-mouse IL-9 monoclonal antibody (clone D9302C12) or its vehicle. A third group was given 50 μg of a monoclonal anti-mouse IL-5 antibody (TRFK-5) or its vehicle. Animals were subsequently exposed to OVA on five days via airways. Newly produced eosinophils were labelled using 5-bromo-2''-deoxyuridine (BrdU). BrdU+ eosinophils and CD34+ cell numbers were examined by immunocytochemistry. After culture and stimulation with OVA or PMA+IC, intracellular staining of IL-9 in bone marrow cells from OVA-exposed animals was measured by Flow Cytometry. The Mann-Whitney U-test was used to determine significant differences between groups.ResultsAnti-IL-9 significantly reduced bone marrow eosinophilia, primarily by decrease of newly produced (BrdU+) and mature eosinophils. Anti-IL-9 treatment also reduced blood neutrophil counts, but did not affect BAL neutrophils. Anti-IL-5 was able to reduce eosinophil numbers in all tissue compartments, as well as BrdU+ eosinophils and CD34+ progenitor cells, and in all instances to a greater extent than anti-IL-9. Also, FACS analysis showed that IL-9 is over-expressed in bone marrow CD4+ cells after allergen exposure.ConclusionsOur data shows that a single dose of a neutralizing IL-9 antibody is not sufficient to reduce allergen-induced influx of newly produced cells from bone marrow to airways. However, in response to allergen, bone marrow cells over-express IL-9. This data suggest that IL-9 may participate in the regulation of granulocytopoiesis in allergic inflammation. |
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