Reversal of gallium arsenide-induced suppression of the antibody-forming cell response by vehicle supernatants. II. Nature and identification of reversing factors.
Previous studies have demonstrated that several immunological events which are T cell mediated are significantly suppressed by a single exposure to gallium arsenide (GaAs). In addition, in the in vitro-generated antibody-forming cell (AFC) response supernatants from vehicle (VH) cultures were able to time-dependently reverse suppression induced by either in vivo (200 mg/kg) or in vitro (50 microM) exposure to GaAs. The present studies were designed to determine the nature and identification of the reversing factors present in VH supernatants. VH supernatants (25-100%) were able to dose-dependently reverse suppression of the AFC response (from 45% suppression to 48% enhancement of the VH response) induced by GaAs exposure (200 mg/kg). Concentration of 24-hr VH supernatants and treatment with proteinases revealed that the reversing factors were protein in nature with a molecular weight between 5,000 and 50,000 Da. This molecular weight range encompasses many of the lymphokines known to be necessary for the generation of an immune response. In antibody cultures exposed either in vivo or in vitro to VH or GaAs, HT-2 bioassay and antigen capture enzyme-linked immunosorbent assays demonstrated that GaAs exposure alters production of interleukin (IL)-2, IL-4, IL-5 and IL-6. Interestingly, the alterations in lymphokine production differed between the exposure regimes. Direct addition of IL-2 to antibody cultures resulted in a dose-dependent (6.25-50 ng/ml) reversal of GaAs-induced suppression (in vivo exposure) and was also dependent on the concentration of GaAs (50-200 mg/kg). IL-4 suppressed the VH AFC response and failed to reverse GaAs suppression.(ABSTRACT TRUNCATED AT 250 WORDS)
Burns
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Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Munson
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D000818:Animals; D000906:Antibodies / Q000378:metabolism; D000921:Antibody-Producing Cells / Q000187:drug effects* / Q000378:metabolism; D001151:Arsenic / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001152:Arsenicals; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D005708:Gallium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008222:Lymphokines / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D012995:Solubility
D000906:Antibodies; D001152:Arsenicals; D017077:Culture Media, Conditioned; D007166:Immunosuppressive Agents; D008222:Lymphokines; C043055:gallium arsenide; D005708:Gallium; D001151:Arsenic