Gallium arsenide exposure impairs processing of particulate antigen by macrophages: modification of the antigen reverses the functional defect.
Gallium arsenide (GaAs), a semiconductor used in the electronics industry, causes systemic immunosuppression in animals. The chemical's impact on macrophages to process the particulate antigen, sheep red blood cells (SRBC), for a T cell response in culture was examined after in vivo exposure of mice. GaAs-exposed splenic macrophages were defective in activating SRBC-primed lymph node T cells that could not be attributed to impaired phagocytosis. Modified forms of SRBC were generated to examine the compromised function of GaAs-exposed macrophages. SRBC were fixed to maintain their particulate nature and subsequently delipidated with detergent. Delipidation of intact SRBC was insufficient to restore normal antigen processing in GaAs-exposed macrophages. However, chemically exposed cells efficiently processed soluble sheep proteins. These findings suggest that the problem may lie in the release of sequestered sheep protein antigens, which then could be effectively cleaved to peptides. Furthermore, opsonization of SRBC with IgG compensated for the macrophage processing defect. The influence of signal transduction and phagocytosis via Fcgamma receptors on improved antigen processing could be dissociated. Immobilized anti-Fcgamma receptor antibody activated macrophages to secrete a chemokine, but did not enhance processing of unmodified SRBC by GaAs-exposed macrophages. Restoration of normal processing of particulate SRBC by chemically exposed macrophages involved phagocytosis through Fcgamma receptors. Hence, initial immune responses may be very sensitive to GaAs exposure, and the chemical's immunosuppression may be averted by opsonized particulate antigens.
Hartmann
Constance B
CB
Department of Microbiology and Immunology, Medical College of Virginia/Virginia Commonwealth University, P.O. Box 980678, Richmond, VA 23298-0678, USA.
McCoy
Kathleen L
KL
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001152:Arsenicals; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005708:Gallium / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D012756:Sheep; D013154:Spleen / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000941:Antigens; D001152:Arsenicals; C043055:gallium arsenide; D005708:Gallium