Induction of terminal differentiation of two variant sublines derived from the human monocytic leukemia cell line THP-1 by all-trans-β-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-γ) and a T-lymphocyte-derived Iymphokine 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 5ʹ-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-γ or DIA.
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