In vitro induction of cytologic and functional differentiation of the immature human monocytelike cell line U-937 with phorbol myristate acetate.
The tumor-promoting ester 4 beta-phorbol 12-myristate 13-acetate (PMA) has been shown to induce the differentiation of the immature monocytelike cell line U-937 c in vitro into a heterogeneous population of cells, including small "dense" cells, large vacuolized or "foamy" cells, spindle-shaped cells, and cells with multiple filopodia ("stellate" cells). The effect of PMA was dose- and time-dependent, the optimal conditions being 40-162 nM PMA for 48 hours. The minimum time of exposure to PMA to ensure further differentiation of U-937 cells was about 5 hours. The PMA-stimulated cells acquired morphologic, ultrastructural, and functional characteristics typical of cells of the monocyte/macrophage lineage. The PMA-treated U-937 cells became adherent, ceased to proliferate, and exhibited increased expression of monocyte-specific antigens (Leu-M2, - M3, HLADr), surface receptors (FcR, C3bR), enzymes (nonspecific esterase, transglutaminase), and ability to mediate chemotaxis, phagocytosis, superoxide anion production, and antibody-dependent cytotoxicity reactions. The induced cells lost their morphologic differentiation and ability to attach to surfaces and regained proliferative capacity upon repeated subculture in PMA-free media.
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D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000032:analysis / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D010587:Phagocytosis / Q000187:drug effects; D010704:Phorbols / Q000494:pharmacology*; D011961:Receptors, Fc / Q000032:analysis; D012397:Rosette Formation; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010704:Phorbols; D011961:Receptors, Fc; D013481:Superoxides; D013755:Tetradecanoylphorbol Acetate