Related Experiment Videos
Antileukoprotease: an endogenous protein in the innate mucosal defense against fungi
J F Tomee1, P S Hiemstra, R Heinzel-Wieland
1Department of Allergology, Groningen University Hospital, Netherlands.
Abstract:
Previous studies have suggested that endogenous protease inhibitors may participate in the mucosal host defense. Antileukoprotease (ALP) is an important protease inhibitor found on various mucosal surfaces, including those of the respiratory and genital tracts. This study reports on the antimicrobial activity of recombinant (r) ALP toward the human fungal pathogens Aspergillus fumigatus and Candida albicans. rALP expressed pronounced fungicidal activity toward metabolically active A. fumigatus conidia and C. albicans yeast cells; however, metabolically quiescent A. fumigatus conidia were totally resistant. In contrast with the protease inhibitory activity of rALP, the fungicidal activity was localized primarily in the NH2-terminal domain. On a molar base, the fungicidal activity of rALP was comparable with that of human defensins and lysozyme. In addition, rALP caused inhibition of C. albicans yeast cell growth. By exhibiting antifungal activity, ALP may play an important role in the innate mucosal defense against human pathogenic fungi.
Insights
Recombinant antileukoprotease (rALP) exhibits significant antifungal activity against active Aspergillus fumigatus and Candida albicans. This protease inhibitor may play a crucial role in innate mucosal defense against fungal infections.
Area of Science:
- Microbiology
- Immunology
- Biochemistry
Background:
- Endogenous protease inhibitors are implicated in mucosal host defense.
- Antileukoprotease (ALP) is a protease inhibitor found on mucosal surfaces like the respiratory and genital tracts.
Purpose of the Study:
- To investigate the antimicrobial activity of recombinant antileukoprotease (rALP) against human fungal pathogens.
- To determine the specific domain responsible for the fungicidal activity of rALP.
Main Methods:
- Recombinant (r) ALP was used to test antimicrobial activity against Aspergillus fumigatus and Candida albicans.
- The fungicidal activity was compared to protease inhibitory activity and localized to the NH2-terminal domain.
- The fungicidal activity of rALP was compared on a molar basis to human defensins and lysozyme.
Main Results:
- rALP demonstrated pronounced fungicidal activity against metabolically active A. fumigatus conidia and C. albicans yeast cells.
- Metabolically quiescent A. fumigatus conidia were resistant to rALP.
- The fungicidal activity of rALP was localized to its NH2-terminal domain and was comparable to defensins and lysozyme.
- rALP also inhibited C. albicans yeast cell growth.
Conclusions:
- Antileukoprotease (ALP) possesses significant antifungal activity against key human pathogens.
- ALP may contribute to innate mucosal immunity by combating fungal infections.
- The NH2-terminal domain of ALP is primarily responsible for its fungicidal properties.