Further development of a flow cytometry assay for identifying and differentiating chemicals known to elicit an irritant, type I, or type IV hypersensitivity response.
Manetz-TS; Munson-AE; Meade-BJ
Toxicologist 1998 Mar; 42(1-S):171
These studies investigated the potential for a single combined irritancyl phenotypic analysis (B220 +. IgE + B220 + ) assay to identify and differentiate chemicals capable of eliciting an irritant. Type I. or Type IV hypersensitivity response. B6C3FI female mice were dermally exposed once daily for four consecutive days with concentrations of TDI (Toluene 2.4-Diisocyanate), TMA (Trimellitic Anhydride) (Type I sensitizers). Dinitroftuorobenzene (DNFB), Oxaz (Oxazolone), and BkCI (Benzalkonium Chloride) (Type IV sensitizers), Tet (Tetradecane) and SLS (Sodium Lauryl Sulfate) (Irritants). Sensitizing doses of TDI, TMA, DNFB, and Oxaz were chosen based on the results of the local lymph node assay. Concentrations of SLS, BkCI, and Tet were based on the results of a mouse ear swelling irritancy assay. For the combined irritancy/phenotyping assay, ear swelling was assessed five days and draining lymph node B cell IgE phenotype ten days following initial dermal chemical exposure. We previously reponed a correlation between increased levels of total serum IgE and the percent of IgE + B220 + cells. Previous studies in this lab and others have shown an elevation in B220 + cells in the lymph nodes of animals exposed to sensitizers but not in those exposed to irritants. In these studies chemicals known to be irritants but not sensitizers were expected to show an increase in percent ear swelling with no significant increase in the percent of either B220 + or IgE + B220 + cells. which occurred with Tet and SLS exposed animals. Type I sensitizers (TMA, ml) showed an elevation in the percentage of B220 + and IgE + B220 + cells. All known Type IV sensitizers tested showed an elevation in B220 + cells with animals exposed to chemicals known to induce slight elevations of IgE (Oxaz, DNFB) showing moderate increases in the percent of IgE + B220 + cells. For the sensitizers. the percent increase in ear swelling correlated with their ability to induce irritation. These preliminary studies indicate that the combined irritancy/phenotyping assay may be a useful screening tool for identifying and differentiating Type I and Type IV hypersensitivity responses.
Phenols; Phenolic-compounds; Lymphatic-system; Lymph-nodes; Animals; Animal-studies; Laboratory-testing; Laboratory-animals; Hypersensitivity
The Toxicologist. Society of Toxicology 37th Annual Meeting, March 1-5,1998, Seattle, Washington