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"Induction of Maturation in Cultured Human Monocytic Leukemia Cells by a Phorbol Diester".1
Shigeru Tsuchiya 2, Yasuko Kobayashi, Yoichi Goto, Hidesada Okumura, Shingi Nakae, Tasuke Konno, and Keiya Tada
Department of Pediatrics [S. T., Y. G., H. O., S. N., T. K., K. T.]
and
Second Department of Anatomy [Y. K.], Tohoku University School of
Medicine, Sendal 980, Japan
Suspension cultures of a human monocytic leukemia cell line, THP-1, were treated with 0.16 to 160 nm 12-O-tetradecanoylphorbol-13-acetate (TPA). In an original cell line, THP-1-O, cultured again from -80° cryopreservation, more than 80% of the cells adhered to the glass substrate with marked morphological change within 3 hr of TPA treatment. Adherent cells became flat and amoeboid in shape, and many microvilli and flaps of the cell surface disappeared. Well-developed Golgi apparatus, rough endoplasmic reticula, and a large amount of free ribosomes were seen in the cytoplasm.
On the other hand, in THP-1-R cells cultured continuously without cryopreservation for 26 months, approximately 80% of the cells adhered to the substrate 48 hr after TPA treatment. Round and ovoid shapes were kept in THP-1-R cells treated with TPA. Surface Fc receptors for immunoglobulin G were present on more than 90% of THP-1-O and THP-1-R cells and were little affected by treatment with TPA. Sixty to 70% of the TPA-treated THP-1-O and THP-1-R cells were able to phagocytize yeasts and immunoglobulin G-coated sheep erythrocytes. Less than 20% of the untreated THP-1 cells were able to phagocytize yeasts and immunoglobulin G-coated sheep erythrocytes.
In histochemical staining, a-naphthyl butyrate esterase was enhanced after treatment with TPA. Lysozyme activity in culture supernatants was not affected by TPA treatment. When exposed to latex beads and TPA, increased 14CO2 production from [1- 14C]glucose in THP-1-O cells was observed. These results indicate that, after treatment with TPA, human monocytic leukemia cells may be converted into mature cells with functions of macrophages.
Footnotes:
1 1 This work was supported in part by a research grant
from the Intractable Disease Division, Public Health Bureau, Ministry of
Health and Welfare, Japan.
2 To whom requests for reprints should be addressed.
Received June 15, 1981. Accepted December 18, 1981. ©1982 American
Association for Cancer Research.
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