title: Kinetics of the angiogenic response in lung endothelium following acute inflammatory injury with bleomycin.
abstract: OBJECTIVE
  Angiogenesis is a central component of normal wound healing but it has not been fully characterized in lung repair following acute inflammatory injury. The current literature lacks vital information pertaining to the extent, timing, and location of this process. This information is necessary for examining mechanisms that drive normal lung repair in resolving acute inflammatory injury. The goal of our study was to formally characterize lung angiogenesis over a time course of bleomycin-induced lung injury.
  
  
  METHODS
  Female C57BL/6 mice age 8-12 weeks were treated with a single dose of intratracheal bleomycin. Total lung endothelial cells were quantified with flow cytometry 0, 7, 14, 21, and 28 days following bleomycin administration, and endothelial cell replication was assessed using bromodeoxyuridine (BrdU) incorporation.
  
  
  RESULTS
  Endothelial cell replication was maximal 14 days after bleomycin administration, while total lung endothelial cells peaked at day 21. Tissue analysis with stereology was performed to measure total lung vascular surface area in bleomycin at day 21 relative to controls and demonstrated a trend toward increased vasculature in the bleomycin group.
  
  
  CONCLUSIONS
  Angiogenesis begins shortly after injury in the bleomycin model and leads to an expansion in the lung endothelial cell population that peaks at day 21. This study offers the first longitudinal examination of angiogenesis following acute inflammatory lung injury induced by bleomycin. Information provided in this study will be vital for further investigating mechanisms of angiogenesis in both normal and abnormal lung repair.
authors.affiliation: 1National Jewish Health, Denver, Colorado, USA.
authors.forename: Zulma X
authors.initials: ZX
authors.lastname: Yunt
authors.forename: Michael P
authors.initials: MP
authors.lastname: Mohning
authors.forename: Lea
authors.initials: L
authors.lastname: Barthel
authors.forename: Mark T
authors.initials: MT
authors.lastname: Kearns
authors.forename: Rubin M
authors.initials: RM
authors.lastname: Tuder
authors.forename: Dallas M
authors.initials: DM
authors.lastname: Hyde
authors.forename: Peter M
authors.initials: PM
authors.lastname: Henson
authors.forename: William J
authors.initials: WJ
authors.lastname: Janssen
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000503:physiopathology*; D000818:Animals; D001761:Bleomycin; D004727:Endothelium / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D008168:Lung / Q000098:blood supply / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D012038:Regeneration
chemical_list: D001761:Bleomycin
keywords: angiogenesis; bleomycin; lung injury; lung repair; pulmonary endothelium; stereology