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Updated: Jul 4, 2025
Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent
Published on: May 8, 2017
In Vivo Near-Infrared Fluorescence Resonance Energy Transfer (NIR-FRET) Imaging of MMP-2 in ALI/ARDS in LPS-Treated
Nuha Alekhmimi1,2, Qasem Ramadan1, Dana Cialla-May2,3
1Alfaisal University, Al Zahrawi Street, Al Maather, Al Takhassusi Rd, Riyadh 11533, Saudi Arabia.
Abstract:
Matrix metalloproteinases (MMPs) are zinc-dependent proteinases that are capable of cleavage of extracellular matrix (ECM) proteins and enzymes and play an important role in lung dysfunction. Specifically, MMP-2 is produced in the lung by alveolar epithelial and endothelial cells and other immune cells, such as macrophages. MMP-2 regulatory pathway is initiated in alveolar macrophages during acute lung injury (ALI), which may increase pulmonary inflammation. Therefore, there is a critical need for fast and reliable techniques to track the acute respiratory distress syndrome (ARDS). Here, we describe near-infrared fluorescence resonance energy transfer (NI-FRET) MMP-2-based probe for the in vivo detection of ALI induced by lipopolysaccharides (LPS). LPS-induced MMP-2 was measured using near-infrared (NIR) imaging after 1, 2, 4, 5, and 24 h of LPS exposure. Our results were compared with the data obtained from ELISA and Western blotting, demonstrating that MMP-2 fluorescence probe provide a promising in vivo diagnostic tool for ALI/ARDS in infected mice.
Insights
Researchers developed a novel near-infrared fluorescence probe to detect matrix metalloproteinase-2 (MMP-2) in acute lung injury (ALI). This tool offers a promising in vivo method for diagnosing ALI and acute respiratory distress syndrome (ARDS).
Area of Science:
- Biomedical imaging
- Pulmonary medicine
- Molecular biology
Background:
- Matrix metalloproteinases (MMPs), particularly MMP-2, are implicated in lung dysfunction and inflammation.
- Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) necessitate rapid and reliable diagnostic methods.
- MMP-2 activation in alveolar macrophages is a key event during ALI.
Purpose of the Study:
- To develop and validate a near-infrared fluorescence resonance energy transfer (NI-FRET) probe for in vivo detection of MMP-2.
- To assess the probe's efficacy in detecting lipopolysaccharide (LPS)-induced ALI in a mouse model.
- To establish a novel diagnostic tool for ALI/ARDS.
Main Methods:
- Development of an MMP-2-specific NI-FRET probe.
- Induction of ALI in mice using lipopolysaccharide (LPS).
- In vivo near-infrared (NIR) imaging to monitor MMP-2 activity over time (1, 2, 4, 5, and 24 hours post-LPS).
- Validation of probe results using ELISA and Western blotting.
Main Results:
- The NI-FRET probe successfully detected elevated MMP-2 levels in vivo following LPS administration.
- MMP-2 fluorescence signals correlated with LPS exposure duration.
- Probe performance was validated against established methods like ELISA and Western blotting.
Conclusions:
- The developed MMP-2-based NI-FRET probe is a sensitive and specific tool for in vivo detection of ALI.
- This probe represents a promising advancement for the early diagnosis of ALI/ARDS.
- The study highlights the potential of NIR imaging for real-time monitoring of lung injury.
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