Binding of the differentiation-inducer, granulocyte-colony-stimulating factor, to responsive but not unresponsive leukemic cell lines.

Abstract

Granulocyte-colony-stimulating factor (G-CSF) is a tissue-derived 25,000 MW glycoprotein that stimulates neutrophilic granulocyte colony formation from murine bone marrow progenitor cells in vitro. It is a potent inducer of terminal differentiation, and a suppressor of stem cell renewal in the murine myelomonocytic leukemic cell line, WEHI-3B. Purified G-CSF was radioiodinated to high specific radioactivity with retention of full biological activity. Iodinated G-CSF bound specifically to WEHI-3B cells, J774 macrophage tumor cells and normal murine bone marrow cells, but not to a variety of other tumor cell lines or murine thymocytes. WEHI-3B cells showed a high affinity for 125I-lableled G-CSF (Kd - 90 nM), but they displayed only a small number of specific receptors (300-700/cell) at 37.degree. C. Other purified CSF showed no competition for binding to these receptors. WEHI-3B (D-), a subline of WEHI-3B that cannot be induced to differentiate by G-CSF, showed no specific binding of this factor, indicating that it is deficient in receptor presentation.