RESUMO
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 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. 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 CD11b blockade. Results were confirmed in recombinant cells incubated with amino-PVA SPIONs and ferumoxtran-10, using T2(*)-weighted 3T MRI. CONCLUSION: 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.
Assuntos
Aterosclerose/diagnóstico , Aterosclerose/metabolismo , Compostos Férricos/metabolismo , Antígeno de Macrófago 1/metabolismo , Animais , Aterosclerose/patologia , Transporte Biológico Ativo , Células CHO , Cricetinae , Cricetulus , Espectroscopia de Ressonância de Spin Eletrônica , Compostos Férricos/farmacocinética , Humanos , Técnicas In Vitro , Ativação de Macrófagos , Antígeno de Macrófago 1/genética , Nanopartículas Metálicas , Monócitos/metabolismo , Monócitos/patologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
Popular theories explaining performance differences between males and females generally predict that females tend to outperform males on certain perceptual and linguistic tasks, while males outperform females on tasks involving visual-spatial skills. 28 males and females were shown commercially available computer-generated 3-dimensional illusions in which the hidden object(s) varied in complexity. Although females reported more prior experience with this form of art, males were about four times faster at identifying the illusions at all levels of difficulty.