title: Increased eosinophil-lineage committed progenitors in the lung of allergen-challenged mice.
abstract: BACKGROUND
  There is increasing evidence that hemopoietic progenitor cells may traffic from bone marrow to sites of allergen exposure in asthma and undergo in situ differentiation, contributing to ongoing airway inflammation. However, the isolation and detailed phenotyping of true CD34 + progenitors from lung tissue during an allergen-induced airway eosinophilia has not been performed.
  
  
  OBJECTIVE
  We attempted to isolate and investigate the in vivo kinetics of hemopoietic progenitor cells and production of eosinophilopoietic mediators in the lung.
  
  
  METHODS
  In a mouse model of allergic airway inflammation, cells were extracted from lung tissue by enzymatic digestion. Total (CD34 + 45 + ) and eosinophil lineage committed (CD34 + 45 + IL-5Ralpha + ) progenitors were enumerated by flow cytometry. Outcome measurements were made 2, 6, 12, 24, 48, and 72 hours and 7 and 14 days after allergen challenge.
  
  
  RESULTS
  Compared with saline control, CD34 + 45 + progenitors were elevated between 6 and 48 hours ( P < .05), attenuated by 72 hours and subsequently increased by 14 days ( P > .05). CD34 + 45 + IL-5Ralpha + progenitors were transiently elevated at 6 hours ( P < .05) before a return to preallergen levels by 12 hours and a subsequent increase at 14 days ( P < .05). Bronchoalveolar lavage eosinophils were increased at 2 hours, peaking at 72 hours ( P < .00625) and declining by 14 days. Both IL-5 and eotaxin levels were increased by 2 hours, peaking at 12 hours ( P < .05) and 24 hours ( P < .05), respectively.
  
  
  CONCLUSIONS
  We propose that the increase in CD34 + 45 + IL-5Ralpha + cells and the eosinophilopoietic mediators IL-5 and eotaxin in the lung after allergen exposure may promote in situ differentiation of eosinophils that contribute to ongoing allergic airway inflammation.
authors.affiliation: Firestone Institute for Respiratory Health, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: David S
authors.initials: DS
authors.lastname: Southam
authors.forename: Natasha
authors.initials: N
authors.lastname: Widmer
authors.forename: Russ
authors.initials: R
authors.lastname: Ellis
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Hirota
authors.forename: Mark D
authors.initials: MD
authors.lastname: Inman
authors.forename: Roma
authors.initials: R
authors.lastname: Sehmi
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000032:analysis / Q000096:biosynthesis; D002631:Chemotactic Factors, Eosinophil / Q000032:analysis / Q000096:biosynthesis; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D042381:Granulocyte Precursor Cells / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology*; D015848:Interleukin-5 / Q000032:analysis / Q000096:biosynthesis; D053666:Interleukin-5 Receptor alpha Subunit; D017493:Leukocyte Common Antigens / Q000032:analysis; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018123:Receptors, Interleukin / Q000032:analysis
chemical_list: D018952:Antigens, CD34; C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; C485918:IL5RA protein, human; D015848:Interleukin-5; D053666:Interleukin-5 Receptor alpha Subunit; D018123:Receptors, Interleukin; D017493:Leukocyte Common Antigens