Eosinophilopoiesis in a murine model of allergic airway eosinophilia: Involvement of bone marrow IL-5 and IL-5 receptor alpha

The airway inflammation in asthma is dominated by eosinophils. The aim of t his study was to elucidate the contribution of newly produced eosinophils i n airway allergic inflammation and to determine mechanisms of any enhanced eosinophilopoiesis, OVA-sensitized BALB/c mice were repeatedly exposed to a llergen via airway route. Newly produced cells were identified using a thym idine analog, 5-bromo-2'-deoxyuridine, which is incorporated into DNA durin g mitosis. Identification of IL-5-producing cells in the bone marrow was pe rformed using FAGS. Bone marrow CD3(+) cells were enriched to evaluate IL-5 -protein release in vitro. Anti-ILS-treatment (TRFK-5) was given either sys temically or directly to the airways. IL-SR-bearing cells were localized by immunocytochemistry. Repeated airway allergen exposure caused prominent ai rway eosinophilia after three to five exposures, and increased the number o f immature eosinophils in the bone marrow. Up to 78% of bronchoalveolar lav age (BAL) granulocytes were 5-bromo-2'-deoxyuridine positive. After three a llergen exposures, both CD3+ and non-CD3 cells acquired from the bone marro w 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. Bo ne marrow cells, but not BAL eosinophils, displayed stainable amounts of th e IL-5R alpha-chain. We conclude that the bone marrow is activated by airwa y allergen exposure, and that newly produced eosinophils contribute to a su bstantial degree to the airway eosinophilia induced by allergen. Airway all ergen 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 fo r anti-IL-5-treatment.