Interleukin-5 induces CD34(+) eosinophil progenitor mobilization and eosinophil CCR3 expression in asthma.
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 microg) or inhaled (15 microg) 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 alpha 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.
Stirling
R G
RG
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom.
van Rensen
E L
EL
Barnes
P J
PJ
Chung
K F
KF
D000328:Adult; D018952:Antigens, CD34 / Q000276:immunology*; D001249:Asthma / Q000097:blood / Q000276:immunology*; D018845:CD11 Antigens / Q000096:biosynthesis; D002465:Cell Movement; D004311:Double-Blind Method; D004804:Eosinophils / Q000276:immunology* / Q000502:physiology; D005260:Female; D006801:Humans; D015848:Interleukin-5 / Q000008:administration & dosage* / Q000494:pharmacology; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D018123:Receptors, Interleukin / Q000096:biosynthesis
D018952:Antigens, CD34; C515350:CCR3 protein, human; D018845:CD11 Antigens; D015848:Interleukin-5; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D018123:Receptors, Interleukin; D017493:Leukocyte Common Antigens