title: Dysregulation of Vascular Endothelial Progenitor Cells Lung-Homing in Subjects with COPD.
abstract: Chronic obstructive pulmonary disease (COPD) is characterized by fixed airflow limitation and progressive decline of lung function and punctuated by occasional exacerbations. The disease pathogenesis may involve activation of the bone marrow stimulating mobilization and lung-homing of progenitor cells. We investigated the hypothesis that lower circulating numbers of vascular endothelial progenitor cells (VEPCs) are a consequence of increased lung-sequestration in COPD. Nonatopic, current or ex-smokers with diagnosed COPD and nonatopic, nonsmoking normal controls were enrolled. Blood and induced sputum extracted primitive hemopoietic progenitors (HPCs) and VEPC were enumerated by flow cytometry. Migration and adhesive responses to fibronectin were assessed. In sputum, VEPC numbers were significantly greater in COPD compared to normal controls. In blood, VEPCs were significantly lower in COPD versus normal controls. There were no differences in HPC levels between the two groups in either compartment. Functionally, there was a greater migrational responsiveness of progenitors from COPD subjects to stromal cell-derived factor-1alpha (SDF-1α) compared to normal controls. This was associated with greater numbers of CXCR4(+) progenitors in sputum from COPD. Increased migrational responsiveness of progenitor cells may promote lung-homing of VEPC in COPD which may disrupt maintenance and repair of the airways and contribute to COPD disease pathogenesis.
authors.affiliation: Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON, Canada L8N 3Z5.
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Salter
authors.affiliation: Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON, Canada L8N 3Z5.
authors.forename: Fizza
authors.initials: F
authors.lastname: Manzoor
authors.affiliation: Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON, Canada L8N 3Z5.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Beaudin
authors.affiliation: Firestone Institute for Respiratory Health, Asthma Research Group, St. Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, ON, Canada L8N 4A6.
authors.forename: Melanie
authors.initials: M
authors.lastname: Kjarsgaard
authors.affiliation: Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON, Canada L8N 3Z5; Firestone Institute for Respiratory Health, Asthma Research Group, St. Joseph's Healthcare, 50 Charlton Avenue East, Hamilton, ON, Canada L8N 4A6.
authors.forename: Parameswaran
authors.initials: P
authors.lastname: Nair
authors.affiliation: Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON, Canada L8N 3Z5.
authors.forename: Gail M
authors.initials: GM
authors.lastname: Gauvreau
authors.affiliation: Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON, Canada L8N 3Z5.
authors.forename: Roma
authors.initials: R
authors.lastname: Sehmi
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002448:Cell Adhesion; D002465:Cell Movement; D066026:Endothelial Progenitor Cells / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000503:physiopathology*; D013183:Sputum / Q000166:cytology* / Q000378:metabolism