A MOUSE MODEL FOR STUDY OF LOCALIZED TOLUENE DIISOCYANATE ADDUCTS FOLLOWING INTRABRONCHIAL ADMINISTRATION OF THE CHEMICAL: INFLAMMATION AND ANTIBODY PRODUCTION

Abstract

Intranasal and intratracheal administration of chemicals are alternative routes to inhalation in some immunologic and toxicologic studies. Selection of an appropriate route frequently depends on the physical-chemical characteristics of the agent, and the desire to avoid aerosol generation. We report a simple surgical procedure for site-specific intrabronchial administration of chemicals as a first step in development of a mouse model of chemical asthma. Toluene diisocyanate (TDI), a recognized cause of occupational asthma, was diluted in corn oil, then administered to the left lung lobe through a cannula. Fifteen days later, mice were challenged by delivery of 1 mug TDI to the same location. Histopathologic examination 24 h later revealed infiltration of lymphocytes, neutrophils, and eosinophils around the vasculature and airways. Macrophages were increased in the alveoli. Similar inflammatory reactions were noted in the treated, nonchallenged animals. Immunostaining using a rabbit antiserum prepared to a TDI-conjugated protein indicated TDI adducts localized to the epithelium of the airways and present only in the lung lobe that received the chemical. Hapten-specific immunoglobulin G (IgG) antibodies were detected in the circulation, but titers were low and did not correspond with the degree of pulmonary inflammation. These results suggest that this procedure is applicable to development of an animal model of chemically induced asthma in which the role of localized exposure can be elucidated.