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Characterization of Active MMP9 in Chronic Inflammatory Diseases Using a Novel Anti-MMP9 Antibody
Maile Velasquez1, Chris O'Sullivan1, Robert Brockett1
1Gilead Sciences, Inc., Foster City, CA 94404, USA.
Abstract:
Matrix metalloproteinase 9 (MMP9), a protease implicated in multiple diseases, is secreted as an inactive zymogen and requires proteolytic removal of the pro-domain for activation. The relative levels and functionality of the pro- and active-MMP9 isoforms in tissues are not characterized. We generated a specific antibody that distinguishes an active form of MMP9, F107-MMP9, from the inactive pro-MMP9 isoform. Using multiple in vitro assays and specimen types, we show that F107-MMP9 expression is localized and disease-specific compared with its more abundant parental pro-form. It is detected around sites of active tissue remodeling, including fistulae of inflammatory bowel and dermal fissures in hidradenitis suppurativa, and is expressed by myeloid cells, including macrophages and neutrophils. Together, our findings provide insights into the distribution and potential role of MMP9 in inflammatory diseases.
Insights
Researchers developed a new antibody to detect active matrix metalloproteinase 9 (MMP9) in tissues. This active form, F107-MMP9, is disease-specific and found at sites of tissue remodeling in inflammatory conditions.
Area of Science:
- Biochemistry
- Immunology
- Pathology
Background:
- Matrix metalloproteinase 9 (MMP9) is a protease involved in various diseases.
- MMP9 is secreted as an inactive zymogen requiring pro-domain removal for activation.
- The tissue distribution and functionality of active versus inactive MMP9 isoforms are not well understood.
Purpose of the Study:
- To develop a specific antibody to differentiate active F107-MMP9 from inactive pro-MMP9.
- To characterize the expression patterns of active MMP9 in disease states.
Main Methods:
- Generation of a specific antibody targeting the active F107-MMP9 isoform.
- In vitro assays using multiple specimen types.
- Immunohistochemical analysis to detect F107-MMP9 localization.
Main Results:
- A novel antibody successfully distinguished active F107-MMP9 from inactive pro-MMP9.
- Active F107-MMP9 expression was localized and disease-specific, unlike the abundant pro-MMP9.
- F107-MMP9 was detected at sites of active tissue remodeling in inflammatory bowel disease and hidradenitis suppurativa.
- Myeloid cells, including macrophages and neutrophils, expressed active MMP9.
Conclusions:
- The study provides a tool to specifically detect active MMP9.
- Active MMP9 is differentially expressed in inflammatory diseases.
- Findings offer insights into MMP9's role in tissue remodeling during inflammation.
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