Interleukin-5 Induces CD34+Eosinophil Progenitor Mobilization and Eosinophil CCR3 Expression in Asthma

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Abstract
Asthma is characterized by the accumulation of activated T cells and eosinophils within the airway. Eosinophils derive from CD34+ bone marrow progenitor cells under the influence of hematopoietic growth factors, subsequently migrating to the airways under the cooperative influence of interleukin (IL)-5 and chemokines, including eotaxin. We compared the relative effects of systemic versus local IL-5 on progenitor-cell mobilization and mature eosinophil phenotype by using flow cytometry, following the administration of intravenous (2 μ g) or inhaled (15 μ g) IL-5 to nine patients with mild asthma. Intravenous IL-5 induced a rapid reduction in circulating eosinophil counts followed by prolonged blood eosinophilia. Both intravenous (p < 0.002) and inhaled (p < 0.05) IL-5 significantly increased CD34+/CD45+ lymphoblastoid eosinophil progenitors. Intravenous IL-5 increased mature eosinophil CCR3 expression from a baseline mean fluorescence intensity (MFI) of 658 ± 51.7 to 995 ± 93.2 at 24 h (p < 0.05), but had no effect on interleukin-5 receptor subunit α or CD11b expression. Lymphocyte CCR3 MFI was increased by intravenous IL-5 from 38.5 ± 13.6 at baseline to 73.6 ± 14.3 at 24 h (p < 0.05). Systemic IL-5 increased circulating eosinophil progenitors, suggesting a key role for systemic IL-5 in eosinophil mobilization. Further, IL-5 causes terminal maturation of the eosinophil by increasing CCR3 expression, potentially affecting CCR3-dependent chemotaxis by eosinophils and lymphocytes.