ANTILEUKOPROTEASE - AN ENDOGENOUS PROTEIN IN THE INNATE MUCOSAL DEFENSE AGAINST FUNGI

Previous studies have suggested that endogenous protease inhibitors ma y participate in the mucosal host defense. Antileukoprotease (ALP) is an important protease inhibitor found on various mucosal surfaces, inc luding 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 exp ressed pronounced fungicidal activity toward metabolically active A. f umigatus conidia and C. albicans yeast cells; however, metabolically q uiescent 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 defensin s and lysozyme. In addition, rALP caused inhibition of C. albicans yea st cell growth. By exhibiting antifungal activity, ALP may play an imp ortant role in the innate mucosal defense against human pathogenic fun gi.