Superparamagnetic iron oxide binding and uptake as imaged by magnetic resonance is mediated by the integrin receptor Mac-1 (CD11b/CD18): implications on imaging of atherosclerotic plaques.
BACKGROUND
Superparamagnetic iron oxide nanoparticles (SPIONs) have been successfully used for magnetic resonance imaging (MRI) of atherosclerotic plaques. Endocytosis into monocytes/macrophages has been proposed as the mechanism for SPION uptake, but a specific receptor has not been identified yet. A potential candidate is the versatile integrin Mac-1 (CD11b/CD18, alphaMbeta2), which is involved in leukocyte adhesion, complement activation and phagocytosis.


RESULTS
Intracellular SPION-accumulation was confirmed in cultured human monocytes using immunohistochemistry and iron staining. Recombinant cells expressing Mac-1 in different activation states as well as human monocytes with or without PMA stimulation were incubated either with an unspecific IgG or a CD11b-blocking antibody. Thereafter, cells were incubated with FITC-labeled amino-covered SPIONs or ferumoxtran-10 SPIONs and signal intensity was quantified by flow cytometry. Depending on the activation status of Mac-1, a significant increase in SPION binding/uptake was observed, independent on surface coating. Furthermore, SPION binding/uptake was significantly reduced after CD11b blockade. Results were confirmed in recombinant cells incubated with amino-PVA SPIONs and ferumoxtran-10, using T2(*)-weighted 3T MRI.


CONCLUSIONS
The integrin Mac-1 is directly involved in SPION binding/uptake. Thus, monocytes abundantly expressing Mac-1 and especially activated monocytes expressing activated Mac-1 may be useful vehicles for high resolution MRI labeling of atherosclerotic plaques.
von Zur Muhlen
C
C
Department of Cardiology & Angiology, University Hospital of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany. constantin.vonzurmuehlen@uniklinik-freiburg.de
von Elverfeldt
D
D
Bassler
N
N
Neudorfer
I
I
Steitz
B
B
Petri-Fink
A
A
Hofmann
H
H
Bode
C
C
Peter
K
K
D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D001693:Biological Transport, Active; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004578:Electron Spin Resonance Spectroscopy; D005290:Ferric Compounds / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D008262:Macrophage Activation; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000378:metabolism*; D053768:Metal Nanoparticles; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D005290:Ferric Compounds; D016177:Macrophage-1 Antigen; D011994:Recombinant Proteins; C000499:ferric oxide