SPECIFIC IGE AND IGG1 RESPONSES TO SUBTILISIN CARLSBERG (ALCALASE) INMICE - DEVELOPMENT OF AN INTRATRACHEAL EXPOSURE MODEL

The primary objective of this study was to examine the feasibility of using a mouse model to evaluate the immunogenicity of proteins as a po tential method to determine occupational exposure guidelines. Mice wer e intratracheally administered a benchmark protein allergen, subtilisi n Carlsberg (Alcalase) in detergent matrix once a week for 4 to 6 week s and specific IgE and IgG1 levels were determined. In all experiments , specific IgE levels were determined by using a rat basophilic leukem ia cell (RBL) release assay, while specific IgG1 was measured by an EL ISA. A good correlation was observed between IgE titers determined by the RBL assay and rat passive cutaneous anaphylaxis assay, Intratrache al administration of protease with detergent matrix was found to resul t in significant IgE and IgG1 responses that were dose related. Deterg ent matrix was found to enhance the Alcalase-specific IgE and IgG1 res ponse when administered by the intratracheal route. The IgG1 response was much more robust, easier to measure, and found to follow the IgE r esponse. These results suggest that a mouse intratracheal model is a f easible approach to examining the immunogenic potency of enzymes using specific IgE or IgG1 as the end points. Additional development and va lidation of the mouse model with other types of proteins will be pursu ed. (C) 1996 Society of Toxicology