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Eosinophils as a source of matrix metalloproteinase-9 in asthmatic airway inflammation
1First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Abstract:
Bronchial asthma is characterized by eosinophil infiltration and tissue remodeling. Matrix metalloproteinases (MMPs) are thought to play critical roles by degradating interstitial matrices in a wide range of lung diseases associated with reorganization of the airway architecture. To investigate whether MMPs are involved in the pathologic processes of bronchial asthma, we examined MMP expression in asthmatic subjects. In situ hybridization revealed abundant expression of MMP-9 (gelatinase B) mRNA in biopsy specimens from asthmatic subjects (n = 5), with an average positive cell distribution of 117.8 +/- 41.1 (mean +/- SEM)/mm2. In contrast, sparse expression of the mRNA (10.8 +/- 4.8 /mm2) was observed in specimens from normal subjects (n = 4). The vast majority of cells expressing the mRNA were eosinophils in asthmatic tissues (92.2 +/- 1.2%). MMP-9 protein, which was confined to the submucosal cells in the normal subjects, was not abundantly expressed in inflammatory cells, but there was positive reactivity for MMP-9 protein in the extracellular matrix. Immunoelectron microscopic analysis showed sparse immunolocalization of MMP-9 in the perinuclear spaces of eosinophils, but not in the granules. These findings suggest the overexpression of MMP-9 by eosinophils in bronchial tissues of asthmatic individuals, and the participation of MMPs in the pathologic changes in asthmatic airways.
Insights
Matrix metalloproteinases (MMPs), specifically MMP-9, are significantly overexpressed in eosinophils within bronchial asthma tissues. This suggests MMPs play a key role in the airway remodeling characteristic of asthma.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Immunology
Background:
- Bronchial asthma involves eosinophil infiltration and tissue remodeling.
- Matrix metalloproteinases (MMPs) are implicated in lung tissue reorganization.
Purpose of the Study:
- To investigate the role of MMPs in the pathological processes of bronchial asthma.
- To examine MMP expression in asthmatic subjects.
Main Methods:
- In situ hybridization to detect MMP-9 mRNA expression in lung biopsy specimens.
- Immunohistochemistry and immunoelectron microscopy to analyze MMP-9 protein localization.
Main Results:
- Abundant MMP-9 mRNA expression was found in asthmatic subjects' tissues, primarily in eosinophils.
- MMP-9 mRNA levels were significantly higher in asthmatic (117.8/mm2) compared to normal subjects (10.8/mm2).
- MMP-9 protein was detected in the extracellular matrix and perinuclear spaces of eosinophils in asthmatic airways.
Conclusions:
- Eosinophils overexpress MMP-9 in bronchial asthma.
- MMPs, particularly MMP-9, likely contribute to the airway remodeling and pathology observed in asthma.