Gallium arsenide stimulates the rapid induction of a modulated inflammatory response in the peritoneum

Gallium Arsenide is a technologically and economically important semiconductor material. As such, it has found wide utilization in both military and commercial applications. However, recent studies have identified GaAs as a carcinogen and immunotoxicant. The systemic immunosuppressive effects of GaAs have been well characterized in mice, and can be predominantly attributed to a loss of antigen presentation capacity by affected macrophages. This loss of function corresponds to a decrease in the activity of various cathepsin proteases. In contrast, antigen presentation at the site of exposure is enhanced above that seen in unexposed mice. In vitro culture of macrophages with GaAs fails to recapitulate the in vivo phenotype, leading to the conclusion that the complete mechanism of GaAs mediated activation requires indirect activation of macrophages by other cells or tissue components found in the microenvironment. This work seeks to ascertain the components and mechanisms which initiate GaAs mediated macrophage activation. Exposure to GaAs crystals prompts the rapid recruitment of blood monocytes to the site of exposure with concomitant upregulation of chemokines and inflammatory cytokines. Changes in cytokine levels could be identified both at the mRNA and protein level, and secreted products were detectable in a variety of bodily fluids. In addition, GaAs exposure redirects a significant portion of the transcriptome, altering the global regulation of macrophage metabolism and function. Alterations in patterns of gene expression elucidate mechanisms for increased cellular activation, antigen processing, and modulation of the inflammatory response. These data define the systems of coordinated gene expression by GaAs and thereby illuminate the mechanisms by which GaAs may affect immune system function and human health.