title: Kinetics of bone marrow eosinophilopoiesis and associated cytokines after allergen inhalation.
abstract: Allergen inhalation is associated with increased eosinophil/basophil progenitors in bone marrow 24 hours after allergen inhalation. This study examined the kinetics of eosinophilopoiesis in dual (n = 14), compared with isolated early, responders (n = 12). Dual responders, in contrast to isolated early responders, develop significant sputum and blood eosinophilia and prolonged airway hyperresponsiveness. Bone marrow aspirates were taken before and 5, 12, 24, and 48 hours after allergen inhalation. In dual responders, increases in interleukin (IL)-3-responsive progenitors were detected as early as 5 hours after allergen inhalation, and IL-5-responsive progenitors were detected at 12 and 24 hours. No changes were detected in isolated early responders. Bone marrow IL-5 protein levels increased at 12 and 24 hours in dual responders only and these increases correlated with increases in IL-5-responsive progenitors. In addition, bone marrow IFN-gamma levels increased in dual responders at 48 hours. These data demonstrate that, in dual responders, there is allergen-induced activation of an eosinophilopoietic process that is rapid and sustained, and a relationship between increased bone marrow IL-5 levels and increased eosinophil production. We propose that after allergen inhalation, time-dependent changes in cytokine levels in the bone marrow control differentiation of eosinophil/basophil progenitors.
authors.affiliation: Asthma Research Group, Firestone Institute for Respiratory Health, St. Joseph's Healthcare, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Dorman
authors.forename: Roma
authors.initials: R
authors.lastname: Sehmi
authors.forename: Gail M
authors.initials: GM
authors.lastname: Gauvreau
authors.forename: Rick M
authors.initials: RM
authors.lastname: Watson
authors.forename: Ronan
authors.initials: R
authors.lastname: Foley
authors.forename: Graham L
authors.initials: GL
authors.lastname: Jones
authors.forename: Judah A
authors.initials: JA
authors.lastname: Denburg
authors.forename: Mark D
authors.initials: MD
authors.lastname: Inman
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
mesh_terms: D000328:Adult; D000485:Allergens / Q000009:adverse effects / Q000276:immunology; D001249:Asthma / Q000097:blood / Q000150:complications / Q000276:immunology*; D001853:Bone Marrow / Q000737:chemistry / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000150:complications / Q000276:immunology; D001985:Bronchial Provocation Tests; D016207:Cytokines / Q000032:analysis / Q000097:blood / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D005541:Forced Expiratory Volume; D006410:Hematopoiesis / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000150:complications; D007249:Inflammation; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D007377:Interleukin-3 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000276:immunology*; D013183:Sputum / Q000737:chemistry / Q000276:immunology; D013997:Time Factors; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000485:Allergens; D016207:Cytokines; D007377:Interleukin-3; D015848:Interleukin-5; D016753:Interleukin-10; D007371:Interferon-gamma