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

Introduction: 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 receptorhas not been identified yet. A potential candidate is the versatile integrin Mac-1 (CD1 1b/CD18, alpha M beta 2), which is involved in leukocyte adhesion, complement activation and phagocytosis. Methods and 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 CD I I b blockade. Results were confirmed in recombinant cells incubated with amino-PVA SPIONs and ferumoxtran-10, using T2*-weighted 3T MRI. Conclusion: The integrin Mac- I is directly involved in SPION binding/uptake. Thus, monocytes abundantly expressing Mac- I and especially activated monocytes expressing activated Mac- I may be useful vehicles for high resolution MRI labeling of atherosclerotic plaques.