Assaying Macrophage Activity in a Murine Model of Inflammatory Bowel Disease Using Fluorine-19 MRI

Overview

Journal Lab Invest

Specialty Pathology

Date 2012 Feb 15

PMID 22330343

Citations 35

Authors

Deepak K Kadayakkara

Sarangarajan Ranganathan

Won-Bin Young

Eric T Ahrens

Affiliations

Soon will be listed here.

Abstract

Macrophages have an important role in the pathogenesis of most chronic inflammatory diseases. A means of non-invasively quantifying macrophage migration would contribute significantly towards our understanding of chronic inflammatory processes and aid the evaluation of novel therapeutic strategies. We describe the use of a perfluorocarbon tracer reagent and in vivo (19)F magnetic resonance imaging (MRI) to quantify macrophage burden longitudinally. We apply these methods to evaluate the severity and three-dimensional distribution of macrophages in a murine model of inflammatory bowel disease (IBD). MRI results were validated by histological analysis, immunofluorescence and quantitative real-time polymerase chain reaction. Selective depletion of macrophages in vivo was also performed, further validating that macrophage accumulation of perfluorocarbon tracers was the basis of (19)F MRI signals observed in the bowel. We tested the effects of two common clinical drugs, dexamethasone and cyclosporine A, on IBD progression. Whereas cyclosporine A provided mild therapeutic effect, unexpectedly dexamethasone enhanced colon inflammation, especially in the descending colon. Overall, (19)F MRI can be used to evaluate early-stage inflammation in IBD and is suitable for evaluating putative therapeutics. Due to its high macrophage specificity and quantitative ability, we envisage (19)F MRI having an important role in evaluating a wide range of chronic inflammatory conditions mediated by macrophages.

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References

Winawer S, Fletcher R, Miller L, Godlee F, Stolar M, Mulrow C . Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology. 1997; 112(2):594-642. DOI: 10.1053/gast.1997.v112.agast970594. View

Helfer B, Balducci A, Nelson A, Janjic J, Gil R, Kalinski P . Functional assessment of human dendritic cells labeled for in vivo (19)F magnetic resonance imaging cell tracking. Cytotherapy. 2010; 12(2):238-50. PMC: 5796768. DOI: 10.3109/14653240903446902. View

Mahida Y . The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Inflamm Bowel Dis. 2000; 6(1):21-33. DOI: 10.1097/00054725-200002000-00004. View

Ohkawara T, Nishihira J, Takeda H, Hige S, Kato M, Sugiyama T . Amelioration of dextran sulfate sodium-induced colitis by anti-macrophage migration inhibitory factor antibody in mice. Gastroenterology. 2002; 123(1):256-70. DOI: 10.1053/gast.2002.34236. View

Partlow K, Chen J, Brant J, Neubauer A, Meyerrose T, Creer M . 19F magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons. FASEB J. 2007; 21(8):1647-54. DOI: 10.1096/fj.06-6505com. View

Reinecker H, Steffen M, Witthoeft T, Pflueger I, Schreiber S, Macdermott R . Enhanced secretion of tumour necrosis factor-alpha, IL-6, and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn's disease. Clin Exp Immunol. 1993; 94(1):174-81. PMC: 1534387. DOI: 10.1111/j.1365-2249.1993.tb05997.x. View

Gordon P, Attridge J . Understanding clinical literature relevant to spontaneous intestinal perforations. Am J Perinatol. 2008; 26(4):309-16. DOI: 10.1055/s-0028-1103514. View

Sartor R . Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases. Am J Gastroenterol. 1997; 92(12 Suppl):5S-11S. View

Kojouharoff G, Hans W, Obermeier F, Mannel D, Andus T, Scholmerich J . Neutralization of tumour necrosis factor (TNF) but not of IL-1 reduces inflammation in chronic dextran sulphate sodium-induced colitis in mice. Clin Exp Immunol. 1997; 107(2):353-8. PMC: 1904573. DOI: 10.1111/j.1365-2249.1997.291-ce1184.x. View

10.

Hitchens T, Ye Q, Eytan D, Janjic J, Ahrens E, Ho C . 19F MRI detection of acute allograft rejection with in vivo perfluorocarbon labeling of immune cells. Magn Reson Med. 2011; 65(4):1144-53. PMC: 3135171. DOI: 10.1002/mrm.22702. View

11.

Sempere G, Martinez Sanjuan V, Medina Chulia E, Benages A, Tome Toyosato A, Canelles P . MRI evaluation of inflammatory activity in Crohn's disease. AJR Am J Roentgenol. 2005; 184(6):1829-35. DOI: 10.2214/ajr.184.6.01841829. View

12.

Flogel U, Ding Z, Hardung H, Jander S, Reichmann G, Jacoby C . In vivo monitoring of inflammation after cardiac and cerebral ischemia by fluorine magnetic resonance imaging. Circulation. 2008; 118(2):140-8. PMC: 2735653. DOI: 10.1161/CIRCULATIONAHA.107.737890. View

13.

Neurath M, Fuss I, Pasparakis M, Alexopoulou L, Haralambous S, Meyer zum Buschenfelde K . Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice. Eur J Immunol. 1997; 27(7):1743-50. DOI: 10.1002/eji.1830270722. View

14.

Blumberg R, Saubermann L, Strober W . Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. Curr Opin Immunol. 2000; 11(6):648-56. DOI: 10.1016/s0952-7915(99)00032-1. View

15.

van Meeteren M, Meijssen M, Zijlstra F . The effect of dexamethasone treatment on murine colitis. Scand J Gastroenterol. 2000; 35(5):517-21. DOI: 10.1080/003655200750023787. View

16.

Srinivas M, Morel P, Ernst L, Laidlaw D, Ahrens E . Fluorine-19 MRI for visualization and quantification of cell migration in a diabetes model. Magn Reson Med. 2007; 58(4):725-34. DOI: 10.1002/mrm.21352. View

17.

Ebner B, Behm P, Jacoby C, Burghoff S, French B, Schrader J . Early assessment of pulmonary inflammation by 19F MRI in vivo. Circ Cardiovasc Imaging. 2010; 3(2):202-10. PMC: 3138443. DOI: 10.1161/CIRCIMAGING.109.902312. View

18.

Xavier R, Podolsky D . Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007; 448(7152):427-34. DOI: 10.1038/nature06005. View

19.

Weinstock J, Blum A, Metwali A, Elliott D, Bunnett N, Arsenescu R . Substance P regulates Th1-type colitis in IL-10 knockout mice. J Immunol. 2003; 171(7):3762-7. DOI: 10.4049/jimmunol.171.7.3762. View

20.

Kim P, Chung E, Yamashita H, Hung K, Mizoguchi A, Kucherlapati R . In vivo wide-area cellular imaging by side-view endomicroscopy. Nat Methods. 2010; 7(4):303-5. PMC: 2849759. DOI: 10.1038/nmeth.1440. View