Synthesis by mouse peritoneal cells of G-CSF, the differentiation inducer for myeloid leukemia cells: stimulation by endotoxin, M-CSF and multi-CSF.

Normal C57BL mouse peritoneal cells were able to synthesize material with the ability to induce differentiation in colonies of the mouse myelomonocytic leukemia cell line, WEHI-3B. The active factor was provisionally identified biochemically as the normal regulator, granulocyte colony-stimulating factor, G-CSF. Thioglycollate-induced peritoneal exudate cells had little or no capacity to synthesize such material. Production of active material was elevated 10-100-fold by exposure of peritoneal cells to endotoxin, detectable elevations being observed after the addition of as little as 0.8 ng/ml. Production of G-CSF was observed using adherent peritoneal macrophages, was a radioresistant process depending on protein synthesis and was not modified by the absence or addition of T-lymphocytes. Addition of unfractionated media containing M-CSF or Multi-CSF, partially purified M-CSF or fully purified Multi-CSF elevated the production of G-CSF by peritoneal cells from both C57BL mice and mice of the endotoxin-unresponsive strain C3H/HeJ, but an involvement of endotoxin in this process could not be excluded absolutely. The experiments provide further evidence that microorganisms and perhaps hemopoietic regulators play an important role in modulating the production of G-CSF and thus have the potentiality to influence the emergence and progressive proliferation of myeloid leukemia populations.