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Regulation of Bone Marrow and Airway CD34⁺ Eosinophils by Interleukin-5

Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Institute of Internal Medicine, and Department of Medical Microbiology and Immunology, Göteborg University, Gothenburg, Sweden; and Department of Pulmonology and Immunology, Kaunas University of Medicine, Kaunas, Lithuania

Address correspondence to: Jan Lötvall, M.D., Ph.D., The Lung Pharmacology Group, Dept. of Respiratory Medicine and Allergology, Göteborg University, Guldhedsgatan 10A, 413 46 Gothenburg, Sweden. E-mail: jan.lotvall{at}mednet.gu.se

The aim of this study was to evaluate the effect of a neutralizing anti–interleukin (IL)-5 monoclonal antibody (TRFK-5) on bone marrow and airway CD34⁺ and immature eosinophils. A focus was to determine the effect of the timing of treatment. Balb/c mice were ovalbumin-sensitized and subsequently exposed to ovalbumin for 5–10 d via airway route. Animals were treated intraperitoneally with TRFK-5 or its isotype control (50 µg) once at different time points. Newly produced eosinophils were labeled using 5-bromo-2'-deoxyuridine (BrdU). BrdU⁺ and CD34⁺ eosinophil numbers were examined by immunocytochemistry. TRFK-5 reduced bone marrow immature eosinophils within 3 d. This effect was closely related to a reduction of BrdU⁺ and CD34⁺ bone marrow eosinophils, and reduced numbers of blood eosinophils. However, bronchoalveolar lavage (BAL) eosinophilia was not attenuated to the same degree. The effect of TRFK-5 was most prominent in the extended allergen-exposure protocol, where the treatment was given in the middle of the exposure, with strongly reduced bone marrow CD34⁺ and immature bone marrow eosinophils, blood eosinophils as well as BAL BrdU⁺ eosinophils, and BAL CD34⁺ eosinophils. These data argue that anti–IL-5 downregulates eosinophilopoiesis within 3 d by action in the bone marrow, by inhibition of the early stages of eosinophil maturation from CD34⁺ cells.

Abbreviations: bronchoalveolar lavage, BAL • 5-bromo-2'-deoxyuridine, BrdU • bovine serum albumin, BSA • ethylenediaminetetraacetic acid, EDTA • interleukin, IL • ovalbumin, OVA • phosphate-buffered saline, PBS • tris-buffered saline, TBS