title: Circulating hematopoietic progenitor cells are decreased in COPD.
abstract: BACKGROUND
  Bone marrow derived progenitor cells participate in the repair of injured vessels. The lungs of individuals with emphysema have reduced alveolar capillary density and increased endothelial apoptosis. We hypothesized that circulating levels of endothelial and hematopoietic progenitor cells would be reduced in this group of patients.
  
  
  OBJECTIVE
  The goal of this study was to measure circulating levels of endothelial progenitor cells (EPCs) and hematopoietic progenitor cells (HPCs) in subjects with COPD and to determine if progenitor levels correlated with disease severity and the presence of emphysema.
  
  
  METHODS
  Peripheral blood mononuclear cells were isolated from 61 patients with COPD and 32 control subjects. Levels of EPCs (CD45(dim) CD34+) and HPCs (CD45(+) CD34(+) VEGF-R2(+)) were quantified using multi-parameter flow cytometry. Progenitor cell function was assessed using cell culture assays. All subjects were evaluated with spirometry and CT scanning.
  
  
  RESULTS
  HPC levels were reduced in subjects with COPD compared to controls, whereas circulating EPC levels were similar between the two groups. HPC levels correlated with severity of obstruction and were lowest in subjects with severe emphysema. These associations remained after correction for factors known to affect progenitor cell levels including age, smoking status, the use of statin medications and the presence of coronary artery disease. The ability of mononuclear cells to form endothelial cell colony forming units (EC-CFU) was also reduced in subjects with COPD.
  
  
  CONCLUSIONS
  HPC levels are reduced in subjects with COPD and correlate with emphysema phenotype and severity of obstruction. Reduction of HPCs may disrupt maintenance of the capillary endothelium, thereby contributing to the pathogenesis of COPD.
authors.affiliation: 1Division of Pulmonary Medicine, Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Janssen
authors.forename: Zulma X
authors.initials: ZX
authors.lastname: Yunt
authors.forename: Alaina
authors.initials: A
authors.lastname: Muldrow
authors.forename: Mark T
authors.initials: MT
authors.lastname: Kearns
authors.forename: Angela
authors.initials: A
authors.lastname: Kloepfer
authors.forename: Lea
authors.initials: L
authors.lastname: Barthel
authors.forename: Donna L
authors.initials: DL
authors.lastname: Bratton
authors.forename: Russell P
authors.initials: RP
authors.lastname: Bowler
authors.forename: Peter M
authors.initials: PM
authors.lastname: Henson
mesh_terms: D000071916:AC133 Antigen; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D002452:Cell Count; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D066026:Endothelial Progenitor Cells / Q000737:chemistry; D005260:Female; D005541:Forced Expiratory Volume; D006023:Glycoproteins / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000502:physiology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000032:analysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000097:blood* / Q000150:complications; D012720:Severity of Illness Index; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis; D014797:Vital Capacity
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; D010455:Peptides; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D017493:Leukocyte Common Antigens
keywords: angiogenesis; emphysema; endothelial progenitor cell