Sungmin Kang1, Ho Won Lee2, Young Hyun Jeon3,4, Thoudam Debraj Singh2, Yun Ju Choi2, Ji Young Park5, Jun Sung Kim6, Hyunseung Lee7, Kwan Soo Hong7, Inkyu Lee8, Shin Young Jeong2, Sang-Woo Lee2, Jeoung-Hee Ha9, Byeong-Cheol Ahn2, Jaetae Lee10,11. 1. Department of Nuclear Medicine, Catholic University of Daegu School of Medicine, Gyeongsan-si, South Korea. 2. Department of Nuclear Medicine, Kyungpook National University School of Medicine, 50 Samduk-dong 2-ga, Chung Gu, Daegu, 700-721, South Korea. 3. Department of Nuclear Medicine, Kyungpook National University School of Medicine, 50 Samduk-dong 2-ga, Chung Gu, Daegu, 700-721, South Korea. jeon9014@gmail.com. 4. Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, 807 Hogukro, Bukgu, Daegu, 702-210, South Korea. jeon9014@gmail.com. 5. Department of Pathology, Kyungpook National University School of Medicine, Daegu, South Korea. 6. R&D Center, Biterials, Goyang-si, 410-050, South Korea. 7. Division of MR Research, Korea Basic Science Institute, Daejeon, South Korea. 8. Department of Endocrinology, Kyungpook National University School of Medicine, Daegu, South Korea. 9. Department of Pharmacology, Kyungpook National University School of Medicine, Daegu, South Korea. 10. Department of Nuclear Medicine, Kyungpook National University School of Medicine, 50 Samduk-dong 2-ga, Chung Gu, Daegu, 700-721, South Korea. jaetae@knu.ac.kr. 11. Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Cheombok-ro, Dong-gu, Daegu, 701-310, Korea. jaetae@knu.ac.kr.
Abstract
PURPOSE: This study aimed to track the migration of primary macrophages labeled with near-infrared (NIR) fluorescent magnetic nanoparticles toward chemically induced acute inflammatory lesions in mice and to visualize the effect of anti-inflammatory drugs on macrophage migration using combined fluorescence and magnetic resonance imaging (FLI/MRI). PROCEDURES: Primary macrophages were labeled with NIR fluorescent magnetic nanoparticles, and labeled cells were injected into mice intravenously. One day later, inflammation was induced by subcutaneous injection of 1% carrageenan (CG) solution to footpads of the right hind leg, and phosphate-buffered saline (PBS) as control treatment was subcutaneously injected to footpad of the left hind leg. To evaluate the effect of drug treatment on macrophage migration, a single dose of dexamethasone (DEX) was intraperitoneally administered to the mice immediately after the induction of inflammation and was followed by combined FLI/MRI at predetermined time points. RESULTS: No difference in cellular viability or phagocytic activity was observed between the labeled and parent macrophages. In vivo optical imaging revealed an increase in FLI signals in CG-injected footpads in a time-dependent manner, but not in PBS-treated footpads. DEX treatment inhibited the migration of the labeled macrophages to the CG-injected footpads, with relative decreases in FLI activity. In accordance with FLI, T2*-weighted MR images showed hypo-intense signals in the CG-injected footpads but not in the PBS-injected footpads. The DEX-treated mice did not show a dark signal loss zone on MR images in the CG-treated paw. CONCLUSIONS: We successfully tracked the migration of macrophages to inflammatory lesions using both FLI and MRI with NIR fluorescent magnetic nanoparticles and demonstrated the inhibitory effects of DEX on macrophage migration to inflammation sites.
PURPOSE: This study aimed to track the migration of primary macrophages labeled with near-infrared (NIR) fluorescent magnetic nanoparticles toward chemically induced acute inflammatory lesions in mice and to visualize the effect of anti-inflammatory drugs on macrophage migration using combined fluorescence and magnetic resonance imaging (FLI/MRI). PROCEDURES: Primary macrophages were labeled with NIR fluorescent magnetic nanoparticles, and labeled cells were injected into mice intravenously. One day later, inflammation was induced by subcutaneous injection of 1% carrageenan (CG) solution to footpads of the right hind leg, and phosphate-buffered saline (PBS) as control treatment was subcutaneously injected to footpad of the left hind leg. To evaluate the effect of drug treatment on macrophage migration, a single dose of dexamethasone (DEX) was intraperitoneally administered to the mice immediately after the induction of inflammation and was followed by combined FLI/MRI at predetermined time points. RESULTS: No difference in cellular viability or phagocytic activity was observed between the labeled and parent macrophages. In vivo optical imaging revealed an increase in FLI signals in CG-injected footpads in a time-dependent manner, but not in PBS-treated footpads. DEX treatment inhibited the migration of the labeled macrophages to the CG-injected footpads, with relative decreases in FLI activity. In accordance with FLI, T2*-weighted MR images showed hypo-intense signals in the CG-injected footpads but not in the PBS-injected footpads. The DEX-treated mice did not show a dark signal loss zone on MR images in the CG-treated paw. CONCLUSIONS: We successfully tracked the migration of macrophages to inflammatory lesions using both FLI and MRI with NIR fluorescent magnetic nanoparticles and demonstrated the inhibitory effects of DEX on macrophage migration to inflammation sites.
Entities:
Keywords:
Acute inflammation; Combined fluorescence and magnetic resonance imaging; Macrophage migration; Near-infrared fluorescent magnetic nanoparticles
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