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Cardiovascular Ultrasound

, 13:1

First Online: 08 January 2015Received: 10 November 2014Accepted: 23 December 2014


BackgroundMacrophages 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.

MethodsLung 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.

ResultsHigh 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.

ConclusionIn 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.

KeywordsAtherosclerosis Ultrasound contrast Macrophage Endothelium Perfluorocarbon AbbreviationsBMMBone marrow derived macrophages

B-modeBrightness mode

FACSFluorescence-activated cell sorting

Mac-1Macrophage-1 antigen

LFA-1Lymphocyte function-associated antigen 1

PBSPhosphate buffer saline

PFHPerfluorohexane C6F14

PSGL-1P-Selectin glycoprotein ligand-1

RaylUnit of acoustic impedance Pa.s-m

TNFTumor necrosis factor

VLA-4Very late antigen-4.

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Autor: Liselotte M Kornmann - Alma Zernecke - Daniëlle MJ Curfs - Ben JA Janssen - Christian Weber - Menno PJ de Winther - Rob


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