コレラ菌抽出物によるIgEの不活化とアナフィラキシーの抑制

抄録

 IgE is known to play a key role in allergy. Mast cells bind IgE via the Fc receptor, FcεRI, and secrete inflammatory mediators via the recognition of allergens bound with IgE. Therefore, IgE is a major target for therapeutic treatment. Previous reports have demonstrated that oligomannose on IgE could be a new target to inhibit allergen function. However, the specific enzyme that modulates IgE for allergy treatment is not yet known. Here, we found that commercial receptor destroying enzyme (RDE) from Vibrio cholerae culture fluid can specifically modulate IgE, not IgG, and inactivate the initiation of anaphylaxis. RDE-treated IgE was unable to find the binding site of bone marrow derived-mast cells (BMMCs), followed by a reduction in the release of histamine and cytokines. We also confirmed that RDE-treated IgE could not induce passive cutaneous anaphylaxis (PCA) in mouse ears. From these results, we consider that RDE modulates the structure of IgE, rendering it unable to cause allergy. To reveal the function of RDE, we focused on the relationship of the modulation and glycosylation of IgE using lectin microarray analysis. We found that RDE-treated IgE significantly reduced the binding to Lycopersicon esculentum lectin (LEL) and Phaseolus vulgaris leucoagglutinin (PHA-L). These results suggest that RDE specifically modulates branched glycans on IgE, which is then rendered unable to induce an allergic response. These findings could be used in the development of a new drug to inhibit the function of IgE.