Variants of a human monocytic leukemia cell line (THP-1): induction of differentiation by retinoic acid, interferon-gamma, and T-lymphocyte-derived differentiation-inducing activity.
Induction of terminal differentiation of two variant sublines derived from the human monocytic leukemia cell line THP-1 by all-trans-beta-retinoic acid (RA) was studied. One of the variants was approximately 10 times more resistant to RA and the other, approximately 10 times more sensitive than the parent THP-1. Differentiation of the RA-resistant variant could be induced by immune interferon (IFN-gamma) and a T-lymphocyte-derived lymphokine of a differentiation-inducing activity (DIA), alone or in combination with 10 nM RA. These induced cells showed many of functional monocyte and/or macrophage characteristics, such as superoxide anion production, phagocytosis, and antibody-dependent cellular cytotoxicity. RA suppressed the expression of Fc receptors, phagocytosis, and 5'-nucleotidase activity of the resistant cells, although not the expression of the sensitive variant. These results indicate that RA-resistant cells can be fully induced to differentiate by the combination of RA and IFN-gamma or DIA.
D000920:Antibody-Dependent Cell Cytotoxicity; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002460:Cell Line; D004351:Drug Resistance; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007942:Leukemia, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008222:Lymphokines / Q000494:pharmacology; D009154:Mutation; D009580:Nitroblue Tetrazolium; D010587:Phagocytosis; D012397:Rosette Formation; D014212:Tretinoin / Q000494:pharmacology*
D007376:Interleukin-2; D008222:Lymphokines; D009580:Nitroblue Tetrazolium; D014212:Tretinoin; D007371:Interferon-gamma