title: Progenitor egress from the bone marrow after allergen challenge: role of stromal cell-derived factor 1alpha and eotaxin.
abstract: BACKGROUND
  CCR3 expression on CD34+ cells mediates migration to eotaxin in vitro. CXCR4 and stromal cell-derived factor (SDF)-1alpha are important for stem cell homing to hemopoietic compartments.
  
  
  OBJECTIVE
  To study chemokine-mediated progenitor cell traffic in allergic inflammation.
  
  
  METHODS
  Bone marrow (BM) aspirates were obtained at baseline from normal subjects; atopic subjects without asthma; and subjects with asthma before, 5 hours after, and 24 hours after allergen inhalation (dual and early responders). Changes in chemokine receptor expression and migration were assessed.
  
  
  RESULTS
  Expression of CXCR4, but not CCR3, on BM CD34+ cells was greater in normal subjects compared with atopic subjects with asthma. Likewise, SDF-1alpha, but not eotaxin, stimulated a greater migrational response by BM CD34+ cells from normal subjects compared with subjects with asthma. For all subjects, a positive correlation was found between intensity of CXCR4 expression and magnitude of CD34+ cell response to SDF-1alpha. Allergen inhalation attenuated both intensity of CXCR4 expression and SDF-1alpha levels in marrow from dual compared with early responders 24 hours postallergen. In contrast, the intensity of CCR3 expression on BM CD34+ cells increased in dual compared with early responders at 24 hours postallergen. In addition, an increase in migrational responsiveness of BM CD34+ cells to eotaxin and a decrease to SDF-1alpha 24 hours postallergen was found in dual responder subjects with asthma.
  
  
  CONCLUSIONS
  After allergen inhalation in subjects with asthma, a downregulation in CXCR4 intensity on BM CD34+ cells and a reduction in BM SDF-1alpha levels may reduce progenitor retention to marrow stroma promoting peripheral egress, possibly mediated by the CCR3/eotaxin axis.
authors.affiliation: Asthma Research Group, Firestone Institute for Respiratory Health, St Joseph's Healthcare, and Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Dorman
authors.forename: Irene
authors.initials: I
authors.lastname: Babirad
authors.forename: Julia
authors.initials: J
authors.lastname: Post
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: Paul M
authors.initials: PM
authors.lastname: O'Byrne
authors.forename: Roma
authors.initials: R
authors.lastname: Sehmi
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D001249:Asthma / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology*; D001985:Bronchial Provocation Tests; D002465:Cell Movement / Q000276:immunology; D054413:Chemokine CCL11; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000276:immunology*; D019743:Chemokines, CXC / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D054397:Receptors, CCR3; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis
chemical_list: D018952:Antigens, CD34; C515456:CCL11 protein, human; C515350:CCR3 protein, human; C515255:CXCL12 protein, human; D054413:Chemokine CCL11; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D054397:Receptors, CCR3; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine