Reversal of gallium arsenide-induced suppression of the antibody-forming cell response by vehicle supernatants. I. Pharmacokinetics after in vitro and in vivo exposure.
Exposure of splenocytes in vivo or in vitro to gallium arsenide (GaAs) dose-dependently suppresses the ability of these cells to produce antibody after in vitro immunization with sheep red blood cells. In addition, it has been demonstrated that GaAs exerts immunosuppressive effects early (36 hr) in the generation of a primary antibody-forming cell (AFC) response. The objective of this study was to determine if the GaAs-induced suppression was produced as a result of a GaAs-induced alteration in the secretion of soluble mediators. Supernatants from in vivo and in vitro vehicle (VH)-exposed splenocyte cultures time-dependently reversed GaAs-induced suppression of the in vitro-generated primary AFC response produced by both in vitro (50 microM) and in vivo (200 mg/kg) exposure to GaAs. Supernatants from in vitro GaAs-exposed cells suppressed the VH response 40, 89 and 93% at 24, 36 and 48 hr, respectively. Using the arsenic-binding compound meso-2,3-dimercaptosuccinic acid (100 microM), it was determined that the suppression of the VH response by supernatants from in vitro GaAs-exposed cultures was confounded by the presence of free arsenic in the in vitro GaAs-exposed culture supernatant. In contrast, suppression of in vivo VH-exposed AFC responses by supernatants from in vivo GaAs-exposed cells was not seen. The time-dependent reversal of immunosuppression produced by in vivo or in vitro exposure to GaAs, by supernatants from in vivo and in vitro VH-exposed cells mimics the reported kinetics of suppression by addition of GaAs to antibody cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
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Burns
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Munson
D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001151:Arsenic / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001152:Arsenicals; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005260:Female; D005708:Gallium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D012995:Solubility; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D004113:Succimer
D001152:Arsenicals; D017077:Culture Media, Conditioned; D007166:Immunosuppressive Agents; C043055:gallium arsenide; D005708:Gallium; D004113:Succimer; D001151:Arsenic