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1
*
The Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Institute of Heart and Lung Diseases, Göteborg University, Gothenburg, Sweden;
Department of Clinical Immunology, Karolinska Hospital, The Karolinska Institute, Stockholm, Sweden; and Departments of
Pathology and Molecular Medicine and
§
Medicine, McMaster University, Hamilton, Canada
The airway inflammation in asthma is dominated by eosinophils. The
aim of this study was to elucidate the contribution of newly produced
eosinophils in airway allergic inflammation and to determine mechanisms
of any enhanced eosinophilopoiesis. OVA-sensitized BALB/c mice were
repeatedly exposed to allergen via airway route. Newly produced cells
were identified using a thymidine analog, 5-bromo-2'-deoxyuridine,
which is incorporated into DNA during mitosis. Identification of
IL-5-producing cells in the bone marrow was performed using FACS. Bone
marrow CD3+ cells were enriched to evaluate IL-5-protein
release in vitro. Anti-IL-5-treatment (TRFK-5) was given either
systemically or directly to the airways. IL-5R-bearing cells were
localized by immunocytochemistry. Repeated airway allergen exposure
caused prominent airway eosinophilia after three to five exposures, and
increased the number of immature eosinophils in the bone marrow. Up to
78% of bronchoalveolar lavage (BAL) granulocytes were
5-bromo-2'-deoxyuridine positive. After three allergen exposures, both
CD3+ and non-CD3 cells acquired from the bone marrow
expressed and released IL-5-protein. Anti-IL-5 given i.p. inhibited
both bone marrow and airway eosinophilia. Intranasal administration of
anti-IL-5 also reduced BAL eosinophilia, partly via local effects
in the airways. Bone marrow cells, but not BAL eosinophils, displayed
stainable amounts of the IL-5R 
-chain. We conclude that the bone
marrow is activated by airway allergen exposure, and that newly
produced eosinophils contribute to a substantial degree to the airway
eosinophilia induced by allergen. Airway allergen exposure increases
the number of cells expressing IL-5-protein in the bone marrow. The
bone marrow, as well as the lung, are possible targets for
anti-IL-5-treatment.
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