Local antibody class switching in the nasal mucosa of mice with TDI rhinitis.
Johnson-VJ; Fluharty-K; Reynolds-JS; Luster-MI; Yucesoy-B
Toxicologist 2008 Mar; 102(1):270
The role of antibodies in the etiology of occupational rhinitis and asthma caused by diisocyanate exposure is controversial. Serum levels of diisocyanate-specific IgE and IgG antibodies are detectable in approximately 30% and 80% of exposed workers, respectively. Importantly, specific IgE antibodies have high specificity for disease whereas specific IgG is present in the serum of exposed workers without disease indicating that these antibodies may be markers of exposure. The low detection prevalence of diisocyanate specific antibodies may be due to methodological limitations or low production and utilization of these antibodies at sites of active inflammation. Therefore, we used a previously developed murine model of TDI rhinitis to test the hypothesis that inhalation of diisocyanate vapor results in antibody class switching at the site of exposure, the nasal mucosa. Antibody class switching involves expression of germline transcripts and activation-induced cytidine deaminase (AICD) leading to recombination and production of a mature immunoglobulin transcripts. We employed PCR-based assays to detect germline and mature immunoglobulin transcripts, AICD and IL-4, a cytokine known to drive the process. Mice with TDI rhinitis showed increased expression of IL-4 and AICD. Strong upregulation of mature transcripts for IgG1 and its corresponding germline transcript were observed in mice with TDI rhinitis. In addition, germline and mature transcripts for IgE were detected in some of the TDI treated mice but not in the control mice. Mature and germline transcripts for IgA were detected in approximately 50% of the control mice and were upregulated in all of mice exposed to TDI. Overall, these results provide evidence that antibody class switching occurs in the nasal mucosa following inhalation of TDI. Determining the specificity of local antibodies and their role in respiratory allergies caused by diisocyanates will be important in protecting the health of potentially exposed workers.
Inhalation-studies; Respiratory-function-tests; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Pulmonary-disorders; Pulmonary-function; Pulmonary-system-disorders; Allergens; Allergic-reactions; Nasal-disorders; Mucous-membranes; Antibody-response
The Toxicologist. Society of Toxicology 47th Annual Meeting and ToxExpo, March 16-20, 2008, Seattle, Washington