Background Members of the alarmin family are key molecules to promote and exacerbate inflammatory responses such as arthritis. Elevated levels of S100A8/S100A9 (MRP8/14) in serum and synovial fluids correlate very well with disease activity in rheumatoid and psoriatric arthritis1. We recently demonstrated that S100A9 is a good biomarker to monitor local inflammatory activities in various inflammatory diseases using in vivo imaging based on labeled antibodie2.
Objectives In our present optical imaging study we used a small molecular compound as specific probe for targeting S100A9 in the acute phase of Collagen-Induced Arthritis (CIA) mouse model. We used a fluorescently-labeled compound (CES-271) which has been described earlier to bind specifically to S100A93.
Methods DBA/1J mice were immunized with bovine type II collagen or PBS emulsified in Complete Freund's Adjuvant. On day 21, mice received a booster injection of collagen dissolved in PBS or only PBS. Mice were scored at least 3 times/ week for the visual appearance of arthritis in the peripheral joints using an 3-point score: 0=normal; 1=mild but definitely visible, erythema and oedema of one digit/toe or limb; 2=erythema and moderate oedema of at least two digits/toe or limb; 3=erythema, severe oedema of the entire paw and/or rigidity. The optical in vivo imaging was done after arthritis was clinically detectable after application of CES271-Cy5.5 by FRI (Bruker In-Vivo FXPro). ProSense750 (Perkin Elmer) was injected as internal control of inflammation. At the end of the experiment, serum was analyzed for S100A8/S100A9 by ELISA and paws were processed for histology.
Results CIA-mice developed clear signs of arthritis in comparison to control mice witch correlates well with optical data and bright field images. In comparison to the non-specific ProSense750 S100A9 ligand CES271-Cy5.5 showed an excellent signal to noise ratio. Furthermore serum and histology data showed a similar pattern of S100A9 expression compared to imaging data.
Conclusions Our in vivo optical imaging study suggest that the novel S100A9-ligand CES271 has as great potential for visualizing the inflammatory activities of arthritis in vivo. Due to the correlation with the S100A9 expression, the new tracer CES271 could provide as new fluorescence imaging method for local diagnosis of inflammatory activity in rheumatoid arthritis patients.
Chan, J, Roth, J, Oppenheim, J, Tracey, K, Vogl, T., Feldmann, M, Horwood, N, & Nanchahal, J. (2012) Alarmins: Awaiting a Clinical Response, J. Clin. Invest. 122, 2711-2719
Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity; Thomas Vogl, Michel Eisenblätter, Tom Völler, Stefanie Zenker, Sven Hermann, Peter van Lent, Andreas Faust, Christiane Geyer, Beatrix Petersen, Kirsten Roebrock, Michael Schäfers, Christoph Bremer & Johannes Roth; Nature communications; 2014; 5:4593; DO: 10: 1038
Björk, P., Björk, A., Vogl, T., Stenström, M., Liberg, D., Olsson, A., Roth, J., Ivars, F. & Leanderson, T. (2009) Identification of human S100A9 as a novel target for treatment of autoimmune disease via their binding to quinoline-3-carboxamides, PLoS Biol. 7, e97d
Disclosure of Interest None declared
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