title: Lung homing of endothelial progenitor cells in humans with asthma after allergen challenge.
abstract: BACKGROUND
  Increased bronchial vascularity is a feature of asthma that can contribute to airflow obstruction and progressive decline in lung function. Angiogenesis is associated with the lung homing and in situ differentiation of endothelial progenitor cells (EPC) in mouse models of asthma. We have previously shown that inhibiting allergen (Ag)-induced recruitment of EPC in sensitized mice attenuated increased bronchial vascularity and development of airway hyperresponsiveness.
  
  
  OBJECTIVE
  We investigated the accumulation of EPC and formation of new blood vessels in the lungs of human subjects with asthma after Ag inhalation challenge.
  
  
  METHODS
  Consenting patients with mild atopic asthma (n = 13) with FEV1 ≥ 70%, methacholine PC20 ≤ 16 mg/ml, and a dual response to Ag were recruited. Sputum levels of EPC were determined by multigating flow cytometry, and lung vascularity was enumerated by immunostaining with von Willebrand factor.
  
  
  RESULTS
  Sputum levels of EPC were determined by multigating flow cytometry and lung vascularity was enumerated by immunostaining with von Willebrand factor. There was a significant increase in sputum EPC levels 24 hours post Ag but not diluent challenge. Similarly, a significant increase in the number and diameter of blood vessels in lung biopsy tissue 24 hours post Ag was observed. In vitro culture of EPC demonstrated the capacity of these cells to differentiate into mature endothelial cells and form tubelike vessel structures. In sputum supernatants, there was a significant increase in CXCR2 agonists, IL-8, and Gro-α 24 hours post Ag. Only Gro-α stimulated a significant EPC migrational response in vitro.
  
  
  CONCLUSIONS
  Our data suggest that increased lung homing of EPC may promote bronchial vascularity in allergic asthmatic responses and that the recruitment of these progenitors maybe orchestrated by CXCR2 chemokines.
authors: Asthma Research Group, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Haruki
authors: H
authors: Imaoka
authors: Navneet
authors: N
authors: Punia
authors: Anam
authors: A
authors: Irshad
authors: Sun
authors: S
authors: Ying
authors: Christopher J
authors: CJ
authors: Corrigan
authors: Karen
authors: K
authors: Howie
authors: Paul M
authors: PM
authors: O'Byrne
authors: Gail M
authors: GM
authors: Gauvreau
authors: Roma
authors: R
authors: Sehmi
mesh_terms: D000328:Adult; D056151:Airway Remodeling / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D002465:Cell Movement / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000276:immunology* / Q000473:pathology; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D020545:Respiratory Mucosa / Q000473:pathology; D013183:Sputum / Q000166:cytology; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D023063:Receptors, Interleukin-8B; D014841:von Willebrand Factor