title: α1-acid glycoprotein disrupts capillary-like tube formation of human lung microvascular endothelia.
abstract: OBJECTIVE
  The acute phase protein, α1-acid glycoprotein, is expressed in the lung, and influences endothelial cell function. We asked whether it might regulate angiogenesis in human lung microvascular endothelia.
  
  
  METHODS
  α1-acid glycoprotein was isolated from human serum by HPLC ion exchange chromatography. Its effects on endothelial cell functions including capillary-like tube formation on Matrigel, migration in a wounding assay, chemotaxis in a modified Boyden chamber, adhesion, and transendothelial flux of the permeability tracer, (14)C-albumin, were tested.
  
  
  RESULTS
  α1-acid glycoprotein dose-dependently inhibited capillary-like tube formation without loss of cell viability. At ≥0.50 mg/mL, it inhibited tube formation >70%, and at 0.75 mg/mL, >97%. α1-acid glycoprotein dose- and time-dependently restrained EC migration into a wound as early as 2 hours, and in washout studies, did so reversibly. It was inhibitory against vascular endothelial growth factor-A and fibroblast growth factor-2-driven migration but failed to inhibit chemotactic responsiveness. When α1-acid glycoprotein was added to preformed tubes, it provoked their almost immediate disassembly. As early as 15 minutes, it induced tube network collapse without endothelial cell-cell disruption. It exerted a biphasic effect on cell adhesion to the Matrigel substrate. At lower concentrations (0.05-0.25 mg/mL), it increased cell adhesion, whereas at higher concentrations (≥0.75 mg/mL) decreased adhesion. In contrast, it had no effect on transendothelial (14)C-albumin flux.
  
  
  CONCLUSIONS
  α1-acid glycoprotein, at concentrations found under physiological conditions, rapidly inhibits endothelial cell capillary-like tube formation that may be explained through diminished cell adhesion to the underlying matrix and/or reversibly decreased cell migration.
authors.affiliation: 1Department of Medicine, Division of Infectious Diseases, University of Maryland, Baltimore, and the VA Maryland Health Care System, Baltimore, Maryland, USA.
authors.forename: Alba
authors.initials: A
authors.lastname: Miranda-Ribera
authors.forename: Antonino
authors.initials: A
authors.lastname: Passaniti
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ceciliani
authors.forename: Simeon E
authors.initials: SE
authors.lastname: Goldblum
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000098:blood supply*; D055806:Microvessels / Q000187:drug effects*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009961:Orosomucoid / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D009961:Orosomucoid
keywords: acute phase response; angiogenesis; endothelium; orosomucoid; α1-acid glycoprotein