GALLIUM-ARSENIDE MODULATES PROTEOLYTIC CATHEPSIN ACTIVITIES AND ANTIGEN-PROCESSING BY MACROPHAGES

Gallium arsenide (GaAs) is a semiconductor utilized in the electronics industry. Chemical exposure of animals causes a local inflammatory re action, but systemic immunosuppression. Mice were administered i.p. 20 0 mg/kg GaAs crystals or latex beads, or vehicle, Five days after expo sure, splenic macrophages were defective, whereas thioglycolate-elicit ed :peritoneal macrophages (PEC) were more efficient in processing the Ag, pigeon cytochrome c, than vehicle control macrophages. Various as pects of the MHC class IT Ag-processing pathway were examined. Both ma crophage populations normally presented a peptide fragment to the CD4( +) T cells. Surface MHC class II expression on the PEC was up-regulate d; but splenic cells had normal MHC class II expression, PEC had eleva ted levels of glutathione and cysteine, major physiologic reducing thi ols, However, the cysteine content of splenic macrophages was diminish ed. Proteolytic activities of aspartyl cathepsin D, and thiol cathepsi ns B and L were decreased significantly in splenic macrophages. On the other hand, thiol cathepsin activities were increased selectively in PEG. Latex bead-exposed PEC were not more potent APC, and their thiol cathepsin activities were unchanged, indicating that phagocytosis and nonspecific irritation were not responsible. The phenotype of PEC dire ctly exposed to GaAs mirrored cytokine-activated macrophages, in contr ast to splenic macrophages from a distant site. Therefore, GaAs exposu re differentially modulated cathepsin activities in splenic macrophage s and PEG, which correlated with their Ag-processing efficiency. Perha ps such distinct alterations may contribute to the local inflammation and systemic immunotoxicity caused by chemical exposure.