Paradoxical effects of gallium arsenide on cathepsin L expression by antigen-presenting cells

Gallium arsenide (GaAs) is an intermetallic semiconductor used in the electronics industry. Although industrial workers risk chemical exposure during the manufacture of GaAs, the human health effects are unknown. However, animal studies have determined that the chemical is a carcinogen and an immunotoxicant. Interestingly, GaAs produces paradoxical immunological effects in vivo depending on anatomical location. Aqueous soluble dissociation products of GaAs exposure cause systemic immunosuppression and impaired antigen processing. Antigen processing is the mechanism by which antigen-presenting cells (APC) degrade antigen and present it to helper T cells in the context of major histocompatibility complex molecules in order to elicit an immune response. Conversely, direct exposure to GaAs particles enhances antigen processing by APC at the site of exposure. Parallel to effects on antigen processing, GaAs also induces paradoxical effects on activity of the lysosomal protease cathepsin L (CathL), which plays an important role in antigen processing. Chemical exposure suppresses CathL activity in splenic APC but augments proteolytic activity at the site of chemical exposure. This study examined the mechanisms by which GaAs modulates CathL activity. Suppressed proteolytic activity was not caused by direct enzymatic inhibition or cellular toxicity. However, exposure to soluble GaAs components suppressed CathL, mRNA expression. In contrast, exposure to particulate GaAs augmented CathL mRNA and protein expression. Therefore, different forms of the chemical produce opposite effects on CathL expression. This is the first study to show that GaAs exposure can modulate gene expression, which may be an important mechanism by which the chemical may adversely affect human health.