Direct exposure to gallium arsenide upregulates costimulatory activity of murine macrophages.
Gallium arsenide (GaAs) is an intermetallic semiconductor compound used in the electronics industry. Acute exposure of animals to GaAs systemically suppresses several immune functions while paradoxically causing inflammation at the exposure site. We investigated the effect of GaAs on costimulatory activity of murine peritoneal macrophages, 5 days after ip exposure. Costimulation by macrophages was determined by activation of CD4(+) helper T cell hybridomas to secrete interleukin-2 in the presence of immobilized monoclonal anti-CD3 antibody. Both peritoneal exudate cells (PEC) and resident peritoneal cells exposed to GaAs provided greater costimulation to the T cells than vehicle control cells. 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 intracellular adhesion molecule-1 (ICAM-1) compared to controls. In addition 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 significantly inhibited T cell activation, demonstrating that the molecules on GaAs-exposed cells were functional. In contrast, GaAs did not upregulate costimulatory molecules on splenic macrophages. These findings suggest that direct GaAs exposure improves macrophage costimulatory activity, possibly by activating the cells, which may contribute to respiratory inflammation caused by inhalation of GaAs particles.
Departments of Anatomy, Medical College of Virginia/Virginia Commonwealth University, Richmond, Virginia 23298, USA.
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Caffrey-Nolan
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McCoy
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005708:Gallium / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation
D001152:Arsenicals; C043055:gallium arsenide; D005708:Gallium