Effects of poly(I,C)-LC on growth and differentiation of normal and malignant myelopoietic progenitor cells.
Polyriboinosinic-polycytidylic acid with poly-L-lysine stabilized with carboxymethylcellulose [poly(I,C)-LC] augmented, in a dose- and time-dependent manner, secretion of colony-stimulating factor (CSF) by peritoneal macrophages (M phi) and bone marrow cells (BMC). Optimal effects were found after 2 days of in vitro culture of the cells with 50 micrograms/ml of poly(I,C)-LC or 14 h to 3 days after a single intraperitoneal injection of 1-2 mg/kg of poly(I,C)-LC into normal mice. The increase in CSF secretion by M phi and BMC was paralleled in vivo by an increase in serum CSF levels, followed by a rise in committed granulocyte and M phi progenitor cells (GM-CFU-C), nucleated BMC, and blood leukocytes of myelomonocytic origin. Poly(I,C)-LC at doses greater than 4 mg/kg, however, were strongly myelosuppressive. In vitro treatment of undifferentiated myelomonocytic leukemia cells from the WEHI-3B cell line with 10-1,000 micrograms/ml of poly(I,C)-LC resulted in a significant increase in CSF secretion by the leukemic cells and a concomitant inhibition of their proliferation. Incubation of cells from the WEHI-3B D+ subline, which differentiate in response to GM-CSF or G-CSF, with 50-100 micrograms/ml poly(I,C)-LC in agar cultures induced in approximately 45% of the leukemic colonies a differentiation into granulocytes and/or M phi. Poly(I,C)-LC, however, had no effect on differentiation of cells from the CSF unresponsive WEHI-3B D- subline. The CSF-inducing biological response modifier poly(I,C)-LC thus has the potential to stimulate growth and differentiation of normal, as well as differentiation of malignant myelopoietic progenitor cells.
D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000494:pharmacology* / Q000031:analogs & derivatives; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives*; D051379:Mice; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011070:Poly I-C / Q000494:pharmacology*; D011107:Polylysine / Q000494:pharmacology* / Q000031:analogs & derivatives
D003115:Colony-Stimulating Factors; D011107:Polylysine; C019531:poly ICLC; D008747:Methylcellulose; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C