Receptor-mediated monocytoid differentiation of human promyelocytic cells by tumor necrosis factor: synergistic actions with interferon- gamma and 1,25-dihydroxyvitamin D3 [published erratum appears in Blood 1988 Jan;71(1):272]

Abstract

Human myeloid leukemia cells respond to various signals by differentiating to more mature cells. This study was designed to evaluate the effects of a mononuclear phagocyte-derived factor, tumor necrosis factor/cachectin (TNF), on the proliferation and differentiation of the human cell lines HL-60 (promyelocytic) and U937 (monoblastic), and to characterize TNF receptors on these cells. TNF had no effect on HL-60 cell growth or thymidine incorporation, but it markedly inhibited that of U937 cells. HL-60 cells treated with TNF formed osteoclast-like polykaryons and developed nonspecific esterase positivity. In a dose-dependent fashion, TNF enhanced HL-60 cell nonspecific esterase activity, H2O2 production, NBT reduction, and acid phosphatase content. Together, TNF and interferon-gamma (IFN-gamma) additively and synergistically caused increases in these activities as well as the expression of HLA-DR and the monocyte antigens LeuM3 (CDw14) and OKM1 (CD11). TNF also synergistically enhanced the differentiating effects of 1,25-dihydroxyvitamin D3. The potentiating actions of D3 of IFN-gamma on the TNF effect were maximal when the two agents were present together throughout the incubation, and pretreatment with TNF augmented the subsequent response to D3, but not IFN-gamma. HL-60 and U937 cells bound 125I-labeled TNF specifically, rapidly, and reversibly with binding constants of 227 and 333 pmol/L and receptors per cell of 4,435 and 6,806 for HL-60 and U937, respectively. Scatchard plots were linear, which suggested single classes of receptors. HL-60 TNF receptors were not changed by a three- day treatment with IFN-gamma or D3. U937 and HL-60 cells internalized and degraded 125I-labeled TNF to comparable degrees. TNF has differing effects on HL-60 and U937 cells that are apparently mediated through comparable high-affinity TNF receptors. The unique responses of different cell types to TNF may be due to postreceptor factors.

Effects of vitamin D on the growth of normal and malignant B-cell progenitors

“…The possibility of enhancing the effects of VD in vitro by combining the hormone with other molecules such as growth factors or other chemotherapic agents has been explored. Recently the synergistic effect of VD with granulocyte‐macrophage colony‐stimulating factor on the differentiation of the human monocytic cell line U937 has been demonstrated [36] with interferon‐gamma and tumour necrosis factor in inducing the monocytoid differentiation of human promyelocytic cells [37], and with IL4 in enhancing its antiproliferative effect on mouse monocytic leukaemia cells [38]. Another approach is to combine VD with other inducers of differentiation presenting a synergistic effect [39].…”

Identification of a cis-Regulatory Element and Putative trans-Acting Factors Responsible for 12-O-Tetradecanoylphorbol-13-Acetate (TPA)-Mediated Induction of Heme Oxygenase Expression in Myelomonocytic Cell Lines

“…HL-60 cells differentiate into functional mature granulocytes when treated with dimethyl sulfoxide (11) or retinoic acid (8), and HL-60 and U-937 cells differentiate into macrophage-like cells when treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) (20,42) or 1,25-dihydroxy-vitamin D3 [1,25(OH)2 D3] (31,35). Furthermore, cytokines, such as gamma interferon (IFN-y) (5,41) and tumor necrosis factor alpha (TNF-a) (55,58), induce the activation of these cells. Human monocytic leukemia cell line THP-1 (57) has been characterized as a more differentiated monocytic cell line than U-937 cells and also has the ability to differentiate into macrophage-like cells * Corresponding author.…”