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In Vivo 19F MR Imaging Cell Tracking of Inflammatory Macrophages and Site-specific Development of Colitis-associated Dysplasia.

ABSTRACT: Purpose To investigate whether the magnitude of in vivo fluorine 19 (19F) magnetic resonance (MR) imaging signal is associated with subsequent development of colitis-associated dysplasia after in situ fluorination of inflammatory macrophages in a mouse model of inflammatory bowel disease (IBD). Materials and Methods Experiments were approved by the institutional animal care and use committee. Mice in the experimental group (n = 10) were administered azoxymethane and dextran sulfate sodium to induce colitis-associated dysplasia. Five mice were in the noninduced control group. Animals were injected with a commercially available perfluorocarbon and were examined in vivo with an 11.7-T MR imager for up to 110 days. Colons were then harvested followed by high-spatial-resolution ex vivo MR imaging. Multiple colon segments with or without 19F signal were histologically graded and were correlated with 19F signal intensity by using a Spearman correlation test. The signal intensity in mice with colitis-associated dysplasia was compared with that in control mice with a two-tailed Mann-Whitney U test. Results Patchy distributions of 19F signal intensity in the colon wall were seen on in vivo and ex vivo images, representing chronic inflammation as shown by immunohistochemistry. Histologic scores of inflammation and site-specific development of colitis-associated dysplasia in the descending colon showed good correlation with normalized 19F signal intensity (r = 0.88, P = .033 for the ascending colon; r = 0.82, P = .006 for the descending colon). A significantly (P = .002) higher normalized 19F signal-to-noise ratio was found at sites that developed dysplasia (mean, 0.58 ± 0.09 [standard deviation]) as compared with sites that did not (mean, 0.17 ± 0.22). Conclusion 19F MR imaging cell tracking of macrophages can be used to assess local inflammation in a mouse model of IBD. The resulting local 19F signal intensity, representing the magnitude of inflammation, has a positive correlation with the development of colitis-associated dysplasia. © RSNA, 2016 Online supplemental material is available for this article.

SUBMITTER: Shin SH

PROVIDER: S-EPMC5207125 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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In Vivo <sup>19</sup>F MR Imaging Cell Tracking of Inflammatory Macrophages and Site-specific Development of Colitis-associated Dysplasia.

Shin Soo Hyun SH Kadayakkara Deepak K DK Bulte Jeff W M JW

Radiology 20160719 1

Purpose To investigate whether the magnitude of in vivo fluorine 19 (<sup>19</sup>F) magnetic resonance (MR) imaging signal is associated with subsequent development of colitis-associated dysplasia after in situ fluorination of inflammatory macrophages in a mouse model of inflammatory bowel disease (IBD). Materials and Methods Experiments were approved by the institutional animal care and use committee. Mice in the experimental group (n = 10) were administered azoxymethane and dextran sulfate so ...[more]

PMID: 27440581

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Project description:BackgroundIncreased CD11c+ Mφ aggravates colonic mucosal injuries in ulcerative colitis (UC) with TSP1 protein increased. The thrombospondin-1 (TSP1) protein which could activate Mφ is closely related to the colonic mucosal damage in UC. Here, we investigated the role of TSP1 in the differentiation of CD11c+ Mφ and the mechanism.MethodsWe analyzed the population characteristics of TSP1 genes using the Genotype-Tissue Expression (GTEx) database, and human serum TSP1 protein was detected with ELISA. DSS-induced colitis rats were used to explore the effects of TSP1 on colonic mucosal inflammation. We analyzed the serum cytokines and tissue histopathology to evaluate the severity of UC. Furthermore, we analysed the main source of TSP1 in colon tissue. In vitro, lamina propria mononuclear cells (LPMC) and CD11c+ lamina propria macrophages (LPMP) was isolated from model rats in vivo. The target of TSP1 protein was assessed by LSKL, CD36 and CD47 interfering plasmids. The proteins, the lysosome, lysosomal activity and Cathepsin E activity, and the migration were detected by western blotting, test kits and Transwell.ResultsThe expression of TSP1 was significantly higher in younger, male, and in the rectum and sigmoid than that in older, females, and colon tissues, and was closely related to the severity of UC. Compared with normal rats, the worse disease activity index (DAI) score, more histological damage, CD11c+ Mφ infiltration, and increased expression of several proinflammatory cytokines was displayed in colitis rats with the elevation of serum TSP1 protein. In vitro, TSP1 protein derived from cmMφ and endothelial cells promoted the migration and the differentiation of CD11c+ Mφ via binding on CD36, rather than the cell proliferation. Furthermore, PRKCQ/NF-κB signaling pathway was activated by CD36. However, the effect of TSP1 protein could be reversed by LSKL in vivo, and LSKL and anti-TSP1 antibody in vitro.ConclusionsTSP1 promotes the migration and the differentiation of CD11c+ LPMP with lysosomal activity limited via activating the CD36-PRKCQ/NF-κB signaling pathway, which aggravates the colonic mucosal inflammatory injuries in UC.

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In Vivo 19F MR Imaging Cell Tracking of Inflammatory Macrophages and Site-specific Development of Colitis-associated Dysplasia.

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In Vivo <sup>19</sup>F MR Imaging Cell Tracking of Inflammatory Macrophages and Site-specific Development of Colitis-associated Dysplasia.

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