Induction of Maturation in Cultured Human Monocytic Leukemia Cells by a Phorbol Diester1

Suspension cultures of a human monocytic leukemia cell line, THP-1, were treated with 0.16 to 160 nw 12-O-tetradecanoylphorbol-13-acetate (TPA). In an original cell line, THP1-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 retÃ-cula,and a large amount of free ribosomes were seen in the cytoplasm. On the other hand, in THP-1-R cells cultured continuously without cryopreserva tion 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 im munoglobulin 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 14CO2production 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 macro phages.