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Molecular imaging reveals time course of matrix metalloproteinase activity in acute cutaneous vasculitis in vivo
Author(s) -
Steingräber Annika Kathrin,
Schelhaas Sonja,
Faust Andreas,
Jacobs Andreas Hans,
Schäfers Michael,
Goerge Tobias
Publication year - 2013
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12253
Subject(s) - in vivo , immunofluorescence , matrix metalloproteinase , pathology , inflammation , chemistry , immune system , vasculitis , medicine , immunology , antibody , biology , biochemistry , disease , microbiology and biotechnology
Matrix metalloproteinases ( MMP s) 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 ( L c V ) and detected a significant MMP signal via immunofluorescence staining. Then, we mimicked L c V 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 C y5.5‐ AF 443. 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, C y5.5‐ AF 443 accumulated in ICV spots in the skin of C57 BL /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 β 2 ‐integrins ( CD 18 −/− ) and (ii) subsequent MMP immunofluorescence staining. These findings let us conclude that MMP accumulation in the acute phase of ICV depends on β 2 ‐mediated leucocyte recruitment. In summary, we show that MMP s are involved in ICV as determined by C y5.5‐ AF 443, a new optical marker to longitudinally and non‐invasively follow MMP activity in acute skin inflammation in vivo .