COMPOUNDS THAT INDUCE AUTOIMMUNITY IN THE BROWN-NORWAY RAT SENSITIZE MAST-CELLS FOR MEDIATOR RELEASE AND INTERLEUKIN-4 EXPRESSION

Brown Norway (BN) rats given mercuric chloride (HgCl2), gold (Au) salt s or D-penicillamine develop a T helper 2 (Th2) cell-mediated autoimmu ne syndrome. The recent observation of tissue injury within 24 h of Hg Cl2 treatment suggested the involvement of a non-T cell. We therefore examined the effect of these compounds on rat mast cells in vitro. Inc ubation of BN rat peritoneal mast cells with HgCl2 enhanced the releas e of serotonin in response to IgE cross-linking agents. Mast cells fro m Lewis rats, a strain not susceptible to the autoimmune syndrome in v ivo, were affected to a lesser extent. The effect was observed with pu rified BN mast cells, suggesting a direct action. Similar effects were seen with D-penicillamine in the presence of copper ions, a combinati on that produces hydrogen peroxide, and Au. HgCl2 caused significant i nduction of interleukin (IL)-4 mRNA in mast cells from BN, but not Lew is rats. The data demonstrate a novel enhancing effect of a number of compounds on mast cell mediator release, and an inducing effect of HgC l2 on mast cell IL-4 expression. These findings are consistent with ou r hypotheses that mast cells may contribute to early tissue injury, an d also, via production of IL-4, may initiate and/or augment, the Th 2 response in the BN rat model of chemical-induced autoimmunity.