Tohoku J. Exp. Med., 2002, 196 (3)

Effects of Novel Phenoxazine Compounds, 2-Amino-4, 4a-
Dihydro-4a, 7-Dimethyl-3H-Phenoxazine-3-One and
3-Amino-1, 4a-Dihydro-4a, 8-Dimethyl-
2H-Phenoxazine-2-One on Proliferation of
Phytohemagglutinin- or Anti-Human
IgM-Activated Human Peripheral
Blood Mononuclear Cells

MAMI AKAZAWA, JUNKO KOSHIBU-KOIZUMI, TOSHIHIKO IWAMOTO, MASARU TAKASAKI,
MICHIO NAKAMURA1 and AKIO TOMODA2

Department of Geriatric Medicine, Tokyo Medical University, Tokyo 160-0032,
1Department of Host-Defense Biochemistry, Institute of Tropical Medicine, Nagasaki University, Nagasaki 852-8102, and
2Department of Biochemistry, Tokyo Medical University, Tokyo 160-0022

We examined the in vitro effects of 2-amino-4, 4a-dihydro-4a, 7-dimethyl-3H-phenoxazine-3-one(Phx 1)and 3-amino-1, 4a-dihydro-4a, 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 3H-thymidine of PHA-activated PBMC by as much as 75% and 40%, respectively, at a concentration of 40 mM. 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 3H-thymidine was rather increased in the presence of 15.8 mM Phx 1 or Phx 2. However, at a higher concentration of Phx 1 or Phx 2 (50 mM), 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.

Keywords —— 2-amino-4, 4a-dihydro-4a, 7-dimethyl-3H-phenoxazine-3-one; 3-amino-1, 4a-dihydro-4a, 8-dimethyl-2H-phenoxazine-2-one; phytohemagglutinin; anti-human IgM; mononuclear cells

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Tohoku J. Exp. Med., 2002, 196, 185-192

Address for reprints; Akio Tomoda, Department of Biochemistry, Tokyo Medical University, Shinjuku 6-1-1, Shinjuku-ku, Tokyo 160-0022, Japan.

e-mail: tomoda@tokyo.ac.jp