title: Echogenic perfluorohexane-loaded macrophages adhere in vivo to activated vascular endothelium in mice, an explorative study.
abstract: BACKGROUND
  Macrophages may concentrate ultrasound contrast agents and exhibit selective adhesion to activated endothelium. The present study investigates in mice the potential of perfluorohexane (PFH) loaded macrophages to act as ultrasound contrast agent with high reflectivity and specifically targeted at (atherosclerotic) vascular lesions.
  
  
  METHODS
  Lung passage was evaluated with a mouse echo scanner after injection, at a slow pace or as a bolus, of varying doses of PFH-loaded and unloaded bone marrow macrophages (BMM) into the jugular vein. The interaction of PFH-loaded and unloaded BMM with TNF-α stimulated carotid artery endothelium after tail vein injection was assessed by means of intravital microscopy.
  
  
  RESULTS
  High doses of jugular vein injected PFH-loaded BMM were visible with ultrasound in the pulmonary artery and detectable in the carotid artery. At intravital microscopy, tail vein injected BMM exhibited rolling and adhesion behavior at the TNF-α stimulated carotid endothelium, similar to that of native blood leukocytes. Rolling behavior was not different between PFH-loaded and unloaded BMM (p = 0.38).
  
  
  CONCLUSIONS
  In vivo, perfluorohexane loaded macrophages pass the pulmonary circulation and appear on the arterial side. Moreover, they roll and adhere selectively to activated endothelium under physiological flow conditions. These findings indicate that perfluorohexane loaded BMM could be used to study processes in vivo where endothelial activation plays a role, such as atherosclerosis.
authors.forename: Liselotte M
authors.initials: LM
authors.lastname: Kornmann
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
authors.forename: Daniëlle M J
authors.initials: DM
authors.lastname: Curfs
authors.forename: Ben J A
authors.initials: BJ
authors.lastname: Janssen
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Menno P J
authors.initials: MP
authors.lastname: de Winther
authors.forename: Robert S
authors.initials: RS
authors.lastname: Reneman
authors.forename: Arnold P G
authors.initials: AP
authors.lastname: Hoeks
authors.affiliation: Department of Biomedical Engineering, Cardiovascular Research Institute Maastricht, Maastricht University, PO Box 616, 6200, Maastricht, MD, The Netherlands. k.reesink@maastrichtuniversity.nl.
authors.forename: Koen D
authors.initials: KD
authors.lastname: Reesink
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D003287:Contrast Media; D004337:Drug Carriers; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging*; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage*; D007275:Injections, Intravenous; D007962:Leukocytes / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011651:Pulmonary Artery / Q000000981:diagnostic imaging*; D014463:Ultrasonography
chemical_list: D003287:Contrast Media; D004337:Drug Carriers; D005466:Fluorocarbons; C078626:perflexane