Human mast cells produce matrix metalloproteinase 9
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Published on: March 30, 2022
1Department of Veterinary Clinic, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.
Abstract:
Extracellular matrix-destructive enzymes, like matrix metalloproteinases (MMP), have been recognized in the process of inflammation and tissue remodeling and repair. The affected tissues often contain markedly increased numbers of mast cells. Although mast cells are capable of activating latent collagenase and proMMP, it has so far been unknown whether human mast cells themselves produce and secrete MMP9. In this study, MMP9 production by cord blood-derived cultured human mast cells and HMC-1 human mast cells was examined by reverse-transcriptase PCR, gelatin zymography and Western blot analysis using an antibody against MMP9. Cultured mast cells and HMC-1 cells treated with phorbol 12-myristate 13-acetate were shown to express MMP9 mRNA, and the cultured conditioned media from these cells showed gelatinolytic activity, identical with MMP9. Immunohistochemical examination was performed to detect MMP9 in tissue mast cells; mast cells localized in the skin, lung and synovial tissue showed strongly positive reactions for MMP9. Thus, these findings indicate that human mast cells can produce MMP9, which might contribute to extracellular matrix degradation and absorption in the process of allergic and nonallergic responses.
Insights
Human mast cells produce matrix metalloproteinase-9 (MMP9). This enzyme may contribute to extracellular matrix degradation in allergic and nonallergic inflammatory responses.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Extracellular matrix (ECM)-degrading enzymes, such as matrix metalloproteinases (MMPs), are implicated in inflammation and tissue remodeling.
- Mast cells are abundant in tissues undergoing inflammation and remodeling.
- While mast cells can activate other MMPs, their own production of MMP9 was previously unestablished.
Purpose of the Study:
- To investigate whether human mast cells produce and secrete matrix metalloproteinase-9 (MMP9).
Main Methods:
- Reverse-transcriptase PCR (RT-PCR) to detect MMP9 mRNA.
- Gelatin zymography to assess enzymatic activity.
- Western blot analysis using an anti-MMP9 antibody.
- Immunohistochemistry to localize MMP9 in tissue mast cells.
Main Results:
- Cultured human mast cells (cord blood-derived and HMC-1) expressed MMP9 mRNA.
- Conditioned media from these cells exhibited MMP9-identical gelatinolytic activity.
- Mast cells in skin, lung, and synovial tissues showed strong positive MMP9 immunoreactivity.
Conclusions:
- Human mast cells are a source of MMP9.
- Mast cell-derived MMP9 may play a role in ECM degradation during allergic and nonallergic inflammatory processes.
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