Effects of novel phenoxazine compounds, 2-amino-4, 4α-dihydro-4α, 7-dimethyl-3H-phenoxazine-3-one and 3-amino-1,4α-dihydro-4α, 8-dimethyl-2H-phenoxazine-2-one on proliferation of phytohemagglutinin- or anti-human IgM-activated human peripheral blood mononuclear cells

We examined the in vitro effects of 2-amino-4,4alpha-dihydro-4alpha, 7-dimethyl-3H-phenoxazine-3-one(Phx 1) and 3-amino-1,4alpha-dihydro-4alpha, 8-dimethyl-2H-phenoxazine-2-one (Phx 2) on the proliferation of phytohemagglutinin (PHA)- or anti-human IgM-activated human peripheral blood mononuclear cells (PBMC). Phx 1 and Phx 2 inhibited the incorporation of H-3-thymidine of PHA-activated PBMC by as much as 75% and 40%, respectively, at a concentration of 40 muM. The inhibition was dependent on the dose of Phx 1 and Phx 2. These results strongly suggest that Phx 1 and Phx 2 inhibit proliferation of T cells, because PHA specifically activates the T cells among PBMC. On the other hand, when PBMC were activated by anti-human IgM, which specifically stimulates B cells, the incorporation of H-3-thymidine was rather increased in the presence of 15.8 muM Phx 1 or Phx 2. However, at a higher concentration of Phx 1 or Phx 2 (50 muM), the incorporation of 3H-thymidine was increased by Phx 1, but was inhibited by Phx 2. These results suggest different effects of Phx 1 and Phx 2 on proliferation of human T and B cells. (C) 2002 Tohoku University Medical Press.