SA3443, a novel cyclic disulfide compound, depresses anti-SRBC antibody-forming cell responses in the mouse through inhibition of antigen-presenting cell activities.
(4R)-Hexahydro-7,7-dimethyl-6-oxo-1,2,5-dithiazocine-4-carboxylic acid (SA3443) is a newly synthesized cyclic disulfide compound which has potential hepatoprotective properties. The effect of SA3443 on the induction of anti-sheep red blood cell (SRBC) plaque (antibody) forming cell (PFC) responses was investigated in vivo and in vitro. SA3443 (approximately 3 mg/kg/day) remarkably decreased the number of anti-SRBC PFC in the spleens of mice immunized with a high dose of SRBC in vivo. The addition of SA3443 (approximately 1 x 10(-7) M) at the initiation of mouse spleen cell cultures in vitro also exerted a significant inhibitory effect on subsequent PFC response to SRBC, and removal of SA3443 after 24 h did not reverse its inhibitory effect. Pre-incubation of isolated adherent spleen cells with SRBC and SA3443 resulted in a similar inhibition of subsequent PFC response, but a pre-incubation of macrophage-depleted cells with SRBC and SA3443 or a pre-incubation of the unseparated spleen cells with SA3443 in the absence of SRBC had no effect. These findings have suggested that SA3443 may depress antibody response through inhibition of macrophage antigen-presenting cell activity.
Sasano
M
M
Central Research Laboratories, Santen Pharmaceutical Co., Osaka, Japan.
Hayashi
M
M
Matsunaga
K
K
Nakata
K
K
Mita
S
S
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects*; D000938:Antigen-Presenting Cells / Q000187:drug effects*; D001392:Azocines / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D004220:Disulfides / Q000008:administration & dosage / Q000494:pharmacology*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D012756:Sheep
D000276:Adjuvants, Immunologic; D001392:Azocines; D004220:Disulfides; C069788:SA 3443