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Inhibition of mite protease (Df-protease) with protease inhibitors
A Matsushima1, Y Kodera, S Ozawa
1Department of Materials Science, Toin University, Yokohama, Japan.
Abstract:
A protease from house dust mite(Dermatophagoides farinae) having high specificity towards a substrate of blood coagulation factor XIIa catalyzes the activation of kallikrein-kinin system in plasma (Takahashi et al., 1990). To prevent the formation of kinin by the mite-protease, inhibition of the protease with its inhibitors was tested in vitro and in vivo. Its kinetic studies revealed that Ki values are 3.9 x 10(-10) M for aprotinin, 3.0 x 10(-9) M for soybean trypsin inhibitor (Kunitz) and 2.5 x 10(-8) M for gabexate mesylate. Enhancement of blood permeability in guinea pigs caused by the protease was markedly suppressed by these inhibitors.
Insights
House dust mite protease activates the kallikrein-kinin system. Inhibitors like aprotinin effectively blocked this mite-protease activity, preventing kinin formation and reducing blood permeability in vivo.
Area of Science:
- Biochemistry
- Immunology
- Allergology
Background:
- House dust mites (Dermatophagoides farinae) possess proteases that can activate biological pathways.
- The kallikrein-kinin system plays a role in inflammatory responses, including changes in blood permeability.
Purpose of the Study:
- To investigate the inhibitory effects of specific protease inhibitors on a house dust mite-derived protease.
- To determine the efficacy of these inhibitors in preventing mite-induced kinin formation and blood permeability enhancement.
Main Methods:
- In vitro kinetic studies to determine inhibition constants (Ki) for various protease inhibitors.
- In vivo experiments in guinea pigs to assess the suppression of protease-induced blood permeability.
Main Results:
- The mite protease specifically activates blood coagulation factor XIIa, leading to kallikrein-kinin system activation.
- Aprotinin, soybean trypsin inhibitor (Kunitz), and gabexate mesylate demonstrated potent inhibition of the mite protease with low Ki values.
- These inhibitors significantly suppressed the enhancement of blood permeability in guinea pigs caused by the mite protease.
Conclusions:
- Protease inhibitors can effectively block the activity of house dust mite proteases.
- Inhibition of mite-induced protease activity prevents kinin formation and associated increases in blood permeability.
- These findings suggest potential therapeutic strategies for managing house dust mite allergies.
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