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Induction of a High Phagocytic Capability in P388D1, a Macrophage-like Tumor Cell Line, by 1,25-Dihydroxyvitamin D₃¹

Department of Membrane Research, The Weizmann Institute of Science, Rehovot, Israel

1,25-Dihydroxyvitamin D₃ [1,25-(OH)₂D₃] was shown to induce a high phagocytic capability in the macrophage-like murine tumor cell line P388D1. Induction of phagocytic capability by 1,25-(OH)₂D₃ was dose-dependent in the range of 0.2 to 5.0 ng/ml, required the continuous presence of the secosteroid in culture, and was reversible. 25-Hydroxyvitamin D₃ was an effective inducer only at about 500 ng/ml, while 24R,25-dihydroxyvitamin D₃ was ineffective. The induction of the high phagocytic capability was neither accompanied by increased synthesis of lysozyme nor closely associated with an inhibitory effect on cellular proliferation. P388D1 cells bound (without ingestion) nonopsonized sheep erythrocytes (sheep RBC), and the binding increased in 1,25-(OH)₂D₃-treated cells. Fc-receptor-mediated binding of immunoglobulin G-coated sheep RBC was not modulated in 1,25-(OH)₂D₃-treated cells. Fc-receptor-mediated binding of immunoglobulin G-coated sheep RBC was not modulated in 1,25-(OH)₂D₃-treated cells, but the cells acquired an Fc-receptor-mediated phagocytic capability that was expressed only when preformed P388D1-sheep RBC rosettes were further exposed to immunoglobulin G. Several differentiation agents of myeloid leukemia cells (including dexamethasone) were not effective in inducing the high-phagocytic phenotype, while retinoic acid was very effective. Different myeloid or macrophage-like tumors (WEHI-265, J774.2, PU-5, and WEHI-3) were variable in their response to 1,25-(OH)₂D₃.

¹ Supported by the Edward D, and Anna Mitchell Research Fund.

² To whom requests for reprints should be addressed, at The Weizmann Institute of Science, Department of Membrane Research, Rehovot 76100, Israel.

Received 1/27/83. Accepted 9/ 8/83.

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