Related Experiment Videos
Proteolytic activation of corneal matrix metalloproteinase by Pseudomonas aeruginosa elastase
K Matsumoto1, N B Shams, L A Hanninen
1Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114.
Abstract:
Purified Pseudomonas aeruginosa elastase cleaved a 65 kDa gelatinase [inactive proenzyme form of matrix metalloproteinase (MMP-2)] from human corneal fibroblasts into a biologically active fragment with an approximate molecular mass of 58 kDa. However, purified pseudomonal alkaline protease did not cleave MMP-2 appreciably. Since activated MMP-2 is known to degrade native type IV, V and VII collagens, all components of the corneal basement membrane or stroma, our results suggest a new role for pseudomonal elastase in the pathogenesis of corneal infection, inflammation and ulceration.
Insights
Pseudomonas aeruginosa elastase activates matrix metalloproteinase-2 (MMP-2) in corneal fibroblasts, suggesting a role in corneal disease. This enzyme degrades key collagen components, contributing to infection and ulceration.
Area of Science:
- Ophthalmology
- Microbiology
- Biochemistry
Background:
- Pseudomonas aeruginosa is a common cause of bacterial keratitis.
- Matrix metalloproteinases (MMPs) play a role in tissue remodeling and degradation.
Purpose of the Study:
- To investigate the role of Pseudomonas aeruginosa proteases in activating matrix metalloproteinase-2 (MMP-2).
- To determine the potential contribution of MMP-2 activation to corneal pathogenesis.
Main Methods:
- Purified Pseudomonas aeruginosa elastase and alkaline protease were used to treat human corneal fibroblasts.
- Cleavage of pro-MMP-2 and activation of MMP-2 were assessed using molecular mass analysis.
Main Results:
- Pseudomonas aeruginosa elastase effectively cleaved inactive pro-MMP-2 into an active 58 kDa fragment.
- Pseudomonal alkaline protease showed minimal cleavage activity against pro-MMP-2.
- Activated MMP-2 degrades collagen types IV, V, and VII, crucial components of the corneal basement membrane and stroma.
Conclusions:
- Pseudomonal elastase is implicated in the activation of MMP-2.
- Activated MMP-2 contributes to the degradation of corneal structural components.
- Pseudomonal elastase may play a significant role in the pathogenesis of Pseudomonas-induced corneal infections, inflammation, and ulceration.