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Updated: May 7, 2026
Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent
Published on: May 8, 2017
Molecular imaging reveals time course of matrix metalloproteinase activity in acute cutaneous vasculitis in vivo
Annika Kathrin Steingräber1, Sonja Schelhaas, Andreas Faust
1Department of Dermatology, University Hospital of Muenster, Muenster, Germany.
Abstract:
Matrix metalloproteinases (MMPs) play a critical role in various pathological conditions including cutaneous inflammation. Thus far, serial assessment of MMP activity in ongoing inflammation is hampered due to technical limitations. Here, we present an innovative method for longitudinal detection of MMP activity by in vivo imaging. First, we analysed skin sections from patients suffering from leucocytoclastic vasculitis (LcV) and detected a significant MMP signal via immunofluorescence staining. Then, we mimicked LcV in mice in a well-studied model of immune complex-mediated vasculitis (ICV). This acute inflammatory process was serially visualized in vivo using the fluorescence-labelled MMP tracer Cy5.5-AF443. The deposition of fluorescence-labelled immune complexes and MMP tracer distribution was visualized repeatedly and non-invasively by fluorescence reflectance imaging. In correlation with the presence of MMP-2 and MMP-9 in immunofluorescence stainings, Cy5.5-AF443 accumulated in ICV spots in the skin of C57BL/6 mice. This tracer accumulation could also be observed in mice equipped with a dorsal skinfold chamber, where microscopic observations revealed an increased recruitment of fluorescence-labelled leucocytes during ICV. The specificity of the MMP tracer was supported by (i) analysis of mice deficient in functional β2 -integrins (CD18(-/-) ) and (ii) subsequent MMP immunofluorescence staining. These findings let us conclude that MMP accumulation in the acute phase of ICV depends on β2 -mediated leucocyte recruitment. In summary, we show that MMPs are involved in ICV as determined by Cy5.5-AF443, a new optical marker to longitudinally and non-invasively follow MMP activity in acute skin inflammation in vivo.
Insights
Researchers developed a new in vivo imaging method to track matrix metalloproteinase (MMP) activity during skin inflammation. This technique visualizes MMPs in immune complex-mediated vasculitis (ICV), aiding in understanding inflammatory processes.
Area of Science:
- Biomedical imaging
- Dermatology
- Immunology
Background:
- Matrix metalloproteinases (MMPs) are crucial in skin inflammation.
- Assessing MMP activity longitudinally in vivo has been challenging due to technical limitations.
Purpose of the Study:
- To develop and validate an innovative in vivo imaging method for longitudinal detection of MMP activity in cutaneous inflammation.
- To investigate the role of MMPs in immune complex-mediated vasculitis (ICV) and their correlation with leukocyte recruitment.
Main Methods:
- Analyzed human skin sections with leucocytoclastic vasculitis (LcV) for MMP signals.
- Developed a mouse model of ICV and used a fluorescence-labeled MMP tracer (Cy5.5-AF443) for in vivo imaging.
- Employed fluorescence reflectance imaging and microscopy in dorsal skinfold chambers; analyzed β2-integrin deficient mice.
Main Results:
- Demonstrated significant MMP signal in LcV patient skin.
- Successfully visualized MMP tracer accumulation in vivo in an ICV mouse model, correlating with MMP-2 and MMP-9 presence.
- Observed increased leukocyte recruitment in ICV, dependent on β2-integrin.
Conclusions:
- Cy5.5-AF443 is a novel optical marker for non-invasive, longitudinal monitoring of MMP activity in acute skin inflammation.
- MMP accumulation in acute ICV is linked to β2-integrin-mediated leukocyte recruitment.
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