Restoration by cyclic guanosine monophosphate and extracellular calcium of butylated hydroxyanisole-suppressed primary murine thymus-dependent antibody response.
The effect of dibutyryl cyclic guanosine monophosphate (dbc-GMP) on butylated hydroxyanisole (BHA)-induced suppression of the primary in vitro thymus-dependent antibody response of BDF1 mouse spleen cultures was studied. When added at 0 hr relative to antigen addition, 1 mg of dbc-GMP (8 mM) restored by greater than 70% the BHA-inhibited primary immunoglobulin (Ig)M plaque-forming cell (PFC) response to sheep erythrocytes (SRBC). The suppression was not reversed by the addition of 50 microgram of dibutryl cyclic adenosine monophosphate (dbc-AMP), which is known to reverse suppressor T-cell activity. The addition of 10 mM extracellular calcium (Ca2+) at the same time as antigen to BHA-inhibited cultures resulted in more than 80% restoration of the anti-SRBC PFC response. Quantitation of c-GMP by radioimmunoassay demonstrated that BHA lowered by 58% the c-GMP content of splenic lymphocytes and abrogated the ability of lipopolysaccharide of E. coli (LPS) to elevate c-GMP levels in splenic lymphocytes. The data suggest that BHA exerts its immunosuppressive effect on the primary in vitro antibody response by inhibiting guanylate cyclase activity and effectively lowering c-GMP levels; exogenous dbc-GMP and Ca2+ can freely reverse the immunosuppressive effect of BHA.
D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D000917:Antibody Formation / Q000187:drug effects*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D006152:Cyclic GMP / Q000494:pharmacology*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D051379:Mice; D012756:Sheep / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000502:physiology*
D000840:Anisoles; D002083:Butylated Hydroxyanisole; D003995:Dibutyryl Cyclic GMP; D006152:Cyclic GMP; D002118:Calcium