DIRECT EXPOSURE TO GALLIUM-ARSENIDE UP-REGULATES COSTIMULATORY ACTIVITY OF MURINE MACROPHAGES

Gallium arsenide (GaAs) is an intermetallic semiconductor compound use d in the electronics industry. Acute exposure of animals to GaAs syste mically suppresses several immune functions while paradoxically causin g inflammation at the exposure site. We investigated the effect of GaA s on costimulatory activity of murine peritoneal macrophages, 5 days a fter ip exposure. Costimulation by macrophages was determined by activ ation of CD4(+) helper T cell hybridomas to secrete interleukin-2 in t he presence of immobilized monoclonal anti-CD3 antibody. Both peritone al exudate cells (PEC) and resident peritoneal cells exposed to GaAs p rovided greater costimulation to the T cells than vehicle control cell s. Resident peritoneal cells exposed to GaAs were also more efficient than latex bead-exposed cells, indicating that phagocytosis alone did not cause the GaAs effect. Double immunofluorescence staining and flow cytometric analysis revealed that GaAs-exposed PEC had increased cell surface expression of costimulatory B7-1 and B7-2 molecules and intra cellular adhesion molecule-1 (ICAM-1) compared to controls. In additio n to these molecules, resident peritoneal macrophages exposed to GaAs also expressed significantly higher levels of heat-stable antigen (HSA ). Monoclonal antibodies specific for these costimulatory molecules si gnificantly inhibited T cell activation, demonstrating that the molecu les on GaAs-exposed cells were functional. In contrast, GaAs did not u pregulate costimulatory molecules on splenic macrophages. These findin gs suggest that direct GaAs exposure improves macrophage costimulatory activity, possibly by activating the cells, which may contribute to r espiratory inflammation caused by inhalation of GaAs particles. (C) 19 98 Academic Press.