CCA [N-(2-carboxyphenyl)-4-chloroanthranilic acid disodium salt], a newly developed immunomodulating drug, suppresses T-cell activation by acting on macrophages.
The cellular mechanism of action of a newly developed drug, CCA, N-(2-carboxyphenyl)-4-chloroanthranilic acid disodium salt, on PHA-, autologous mixed lymphocyte reaction (AMLR)-, and phorbol myristate acetate (PMA)-stimulated T-cell proliferation was investigated. Addition of 50 micrograms of CCA per milliliter suppressed PHA- and AMLR-stimulated T-cell proliferation. In contrast, CCA failed to suppress PMA-stimulated macrophage-depleted T-cell proliferation. After treatment of T cells or macrophages with CCA for 12 h, recombined T cells and macrophages were stimulated with phytohemagglutinin. [3H]Thymidine incorporation by T cells was suppressed when macrophages but not T cells were treated with CCA. These results indicate that CCA suppresses T-cell proliferation by acting on macrophages. The mechanism involved in this suppression of CCA was due to the loss of Ia antigen on macrophages and the loss of interleukin-1 (IL-1) secretion from macrophages.
Takeuchi
T
T
Department of Internal Medicine, Saitama Medical Center, Japan.
Koide
J
J
Hosono
O
O
Takano
M
M
Abe
T
T
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D010835:Phytohemagglutinins; D062367:ortho-Aminobenzoates; D003208:Concanavalin A; C015735:lobenzarit; D013755:Tetradecanoylphorbol Acetate