title: Eotaxin-2 regulates newly produced and CD34 airway eosinophils after allergen exposure.
abstract: BACKGROUND
  Eosinophils develop from CD34+ bone marrow progenitors, and evidence increasingly suggests that these progenitors are recruited to the airways in atopic asthmatics after allergen challenge. Moreover, it has been shown that the number of CD34+ progenitors in bronchial tissue correlates with asthma severity. To date, however, little is known about how these cells are recruited into the airways.
  
  
  OBJECTIVE
  Our aim was to evaluate the role of 2 chemokines, eotaxin-I and/or eotaxin-2, in the recruitment of newly produced and CD34+ eosinophils to the airways after allergen exposure.
  
  
  METHODS
  BALB/c mice sensitized and exposed to ovalbumin were pretreated intraperitoneally or intranasally with a neutralizing anti-eotaxin-1 and/or anti-eotaxin-2 antibody.A thymidine analogue, 5-bromo-2'-deoxyuridine (BrdU), was used to mark newly produced cells. Bronchoalveolar lavage (BAL), blood, and bone marrow were collected 24 hours after the final exposure.
  
  
  RESULTS
  Anti-eotaxin-1 and/or anti-eotaxin-2 given intranasally(ie, locally to airways) significantly decreased BAL eosinophils. This decrease was paralleled with a decrease in both BrdU+and CD34+ eosinophils. In contrast, systemically administered(ie, intraperitoneally) anti-eotaxin-1 and/or anti-eotaxin-2 resulted in a significant decrease in BAL eosinophils only when the combined treatment was of a sufficiently high dosage to produce measurable concentrations in the airways.Furthermore, neither of the treated groups showed any significant decrease in blood or bone marrow eosinophils.
  
  
  CONCLUSIONS
  Both eotaxin-1 and eotaxin-2 are involved locally within the airways in the regulation of the recruitment of newly produced and CD34+ eosinophils after allergen exposure.
authors.affiliation: Lung Pharmacology Group, Department of Respiratory Medicine and Allergology, Institute of Internal Medicine, Göteborg University, Guldhedsgatan 10A, SE-413 46 Gothenburg, Sweden.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Rådinger
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Johansson
authors.forename: Brigita
authors.initials: B
authors.lastname: Sitkauskiene
authors.forename: Margareta
authors.initials: M
authors.lastname: Sjöstrand
authors.forename: Jan
authors.initials: J
authors.lastname: Lötvall
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D018952:Antigens, CD34 / Q000032:analysis*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D019742:Chemokines, CC / Q000502:physiology*; D004802:Eosinophilia / Q000209:etiology*; D004804:Eosinophils / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000502:physiology
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D018952:Antigens, CD34; C515457:Ccl11 protein, mouse; C515485:Ccl24 protein, mouse; C515351:Ccr3 protein, mouse; D054413:Chemokine CCL11; D054423:Chemokine CCL24; D019742:Chemokines, CC; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D001973:Bromodeoxyuridine