INDUCTION OF MATURATION IN CULTURED HUMAN MONOCYTIC LEUKEMIA-CELLS BY A PHORBOL DIESTER

Abstract

Suspension cultures of a human monocytic leukemia cell line, THP-1, were treated with 0.16-160 nM 12-O-tetradecanoylphorbol-13-acetate (TPA). In an original cell line, THP-1-O, cultured again from -80.degree. cryopreservation, > 80% of the cells adhered to the glass substrate with marked morphological change within 3 h 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. In THP-1-R cells cultured continuously without cryopreservation for 26 mo., .apprx. 80% of the cells adhered to the substrate 48 h after TPA treatment. Round and ovoid shapes were kept in THP-1-R cells treated with TPA. Surface Fc receptors for IgG were present on > 90% of THP-1-O and THP-1-R cells and were little affected by treatment with TPA. Of the TPA-treated THP-1-O and THP-1-R cells 60-70% were able to phagocytize yeasts and IgG-coated sheep erythrocytes. Of the untreated THP-1 cells < 20% were able to phagocytize yeasts and IgG-coated sheep erythrocytes. In histochemical staining, .alpha.-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. After treatment with TPA, human monocytic leukemia cells may be converted into mature cells with functions of macrophages.