Alkaline Serine Proteinase from <i>Aspergillus fumigatus</i> Has Synergistic Effects on Asp-f-2-Induced Immune Response in Mice

Abstract

Background: Exposure to Aspergillus fumigatus allergens results in the sensitization and the development of allergic bronchopulmonary aspergillosis in susceptible individuals. Aspergillus antigen consists of a number of chemically diverse components and their cumulative or synergistic effect may result in disease. When mice were challenged with individual recombinant allergens, there was only reduced inflammation and immunological responses compared to the whole antigen. Various enzymes identified from A. fumigatus have been thought to cause airway damage. In the present study, we evaluated the effect of exposure to Asp f 13, an alkaline serine proteinase, and Asp f 2 in mice. Methods: BALB/c mice were challenged intranasally with Asp f 2 and Asp f 13 alone and in combination. The antibody response, pulmonary inflammation, and airway hyperreactivity were studied. Results: Results demonstrated no major difference in antibody response and airway responses among the different groups. The inflammatory responses in the lungs, however, showed marked differences in the various groups. Conclusion: In spite of the similar immunological responses in the different groups of mice studied, the results demonstrate enhanced inflammation in the lungs of mice exposed to a combination of both allergens. Allergens with proteinase activity have been found to be involved in airway inflammation and remodeling, which may also apply for Aspergillus-induced allergy.

Profile of Gene Expression in a Murine Model of Allergic Bronchopulmonary Aspergillosis

“…All the Aspergillus-immunized mice showed significant histological changes similar to ABPA, while all controls were normal (6). As reported previously in a series of communications, the antibody and eosinophil responses as well as histological and immunohistochemical findings in the A. fumigatus-exposed mice were comparable to responses in human ABPA (3,(6)(7)(8).…”

TheAspergillus fumigatusStuA Protein Governs the Up-Regulation of a Discrete Transcriptional Program during the Acquisition of Developmental Competence

“…Finally, clock-controlled gene 9 encodes a trehalose synthase required for normal conidiation in response to light cycling in N. crassa (Shinohara et al, 2002) Several other stuA-dependent developmental genes are predicted to encode proteins that are involved in the immune response to A. fumigatus during allergic or invasive disease. The elaboration of IgE-binding proteins by A. fu- migatus (including rAsp f13, an alkaline serine protease; and IgE-binding protein Afu6g00430) is a key stimulus for the development of allergic bronchopulmonary aspergillosis (Kurup et al, 2002;Stevens et al, 2003), suggesting that StuAp may play an important role in the pathogenesis of this condition. MP2 encodes a surface protein in A. fumigatus that elicits a specific antibody response during invasive disease, although its role in protective or allergic immunity has Comparative expression of genes comprising the stuA-dependent putative biosynthetic cluster, arranged by genomic location.…”

Pharmacological Targeting of Anaphylatoxin Receptors during the Effector Phase of Allergic Asthma Suppresses Airway Hyperresponsiveness and Airway Inflammation

“…Active proteases represent a critical biochemical activity underlying intrinsic AF allergenicity that is missing in OVA. Such proteases are able to cleave local C3 and C5 to generate C3a and C5a (45). Further, AF can activate the complement cascade by the lectin pathway (46).…”