Dataset Information
Imaging Granzyme B Activity Assesses Immune-Mediated Myocarditis.
Ontology highlight
ABSTRACT: Rationale
The development of molecular imaging approaches that assess specific immunopathologic mechanisms can advance the study of myocarditis.Objective
This study validates a novel molecular imaging tool that enables the in vivo visualization of granzyme B activity, a major effector of cytotoxic CD8+ T lymphocytes.Methods and results
We synthesized and optimized a fluorogenic substrate capable of reporting on granzyme B activity and examined its specificity ex vivo in mice hearts with experimental cytotoxic CD8+ T lymphocyte-mediated myocarditis using fluorescence reflectance imaging, validated by histological examination. In vivo experiments localized granzyme B activity in hearts with acute myocarditis monitored by fluorescent molecular tomography in conjunction with coregistered computed tomography imaging. A model anti-inflammatory intervention (dexamethasone administration) in vivo reduced granzyme B activity (vehicle versus dexamethasone: 504±263 versus 194±77 fluorescence intensities in hearts; P=0.002).Conclusions
Molecular imaging of granzyme B activity can visualize T cell-mediated myocardial injury and monitor the response to an anti-inflammatory intervention.
SUBMITTER: Konishi M
PROVIDER: S-EPMC4553143 | biostudies-literature | 2015 Aug
REPOSITORIES: biostudies-literature
Publications
Imaging Granzyme B Activity Assesses Immune-Mediated Myocarditis.
Circulation research 20150721 6
<h4>Rationale</h4>The development of molecular imaging approaches that assess specific immunopathologic mechanisms can advance the study of myocarditis.<h4>Objective</h4>This study validates a novel molecular imaging tool that enables the in vivo visualization of granzyme B activity, a major effector of cytotoxic CD8+ T lymphocytes.<h4>Methods and results</h4>We synthesized and optimized a fluorogenic substrate capable of reporting on granzyme B activity and examined its specificity ex vivo in m ...[more]