title: Interleukin-4 and interleukin-13 prime migrational responses of haemopoietic progenitor cells to stromal cell-derived factor-1α.
abstract: BACKGROUND
  Lung-homing of progenitor cells is associated with inflammatory and remodelling changes in asthma. Factors that modulate the increased traffic of progenitor cells to the site of inflammation in asthma remain to be defined. Interleukin (IL)-4 and IL-13 are Th2 cytokines that are key regulators of asthma pathology.
  
  
  OBJECTIVE
  We investigated the role of IL-4 and IL-13 in modulating the trans-migrational responses of haemopoietic progenitor cells (HPC).
  
  
  METHODS
  HPC were enriched from cord blood (CB) and peripheral blood (PB) samples. Migration of HPC was assessed using transwell migration assays, and responding cells were enumerated by flow cytometry.
  
  
  RESULTS
  IL-4 and IL-13 primed migration of CB- and PB-derived HPC (CD34(+) 45(+)  cells) to stromal cell-derived factor-1α (SDF-1α), in vitro. However, these cytokines had no effect on migrational responses of eosinophil-lineage committed progenitors (CD34(+) 45(+) IL-5Rα(+)  cells) or mature eosinophils to SDF-1α. For HPC, priming effects of IL-4 (0.1 ng/mL) and IL-13 (0.1 ng/mL) were detectable within 1 h and optimal at 18-h post-incubation, and IL-4 was the more effective priming agent. Pre-incubation with IL-4 or IL-13 had no effect on the intensity of cell surface expression of SDF-1α receptor, CXCR4. Disruption of cell membrane cholesterol content by pre-incubation with polyene antibiotics inhibited IL-4 priming of SDF-1α stimulated migration of HPC indicating that increased incorporation of CXCR4 into membrane lipid rafts mediated the cytokine primed migrational response of HPC. This was confirmed by confocal fluorescent microscopy.
  
  
  CONCLUSIONS
  IL-4 and IL-13 prime the migrational response of HPC to SDF-1α by enhancing the incorporation of CXCR4 into lipid rafts. The priming effect of these cytokines is specific to primitive HPC. These data suggest that increased local production of IL-4 and IL-13 within the lungs may promote increased SDF-1α mediated homing of HPC to the airways in asthma.
authors.affiliation: Firestone Institute for Respiratory Health, Asthma Research Group, St Joseph's Healthcare, Hamilton, ON, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Punia
authors.forename: S
authors.initials: S
authors.lastname: Smith
authors.forename: J V
authors.initials: JV
authors.lastname: Thomson
authors.forename: A
authors.initials: A
authors.lastname: Irshad
authors.forename: P
authors.initials: P
authors.lastname: Nair
authors.forename: R
authors.initials: R
authors.lastname: Sehmi
mesh_terms: D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018793:Interleukin-13 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000276:immunology; D013997:Time Factors
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; C508598:IL4 protein, human; D018793:Interleukin-13; D019718:Receptors, CXCR4; D015847:Interleukin-4