Evidences That Fibroblasts and Epithelial Cells Produce a Specific Type of Macrophage and Granulocyte Inducer, Also Known as Colony- Stimulating Factor, and That Monocyte- Macrophages Can Produce Another Factor with Proliferative Inducing Activity on Myeloid Cells and Differentiative Activity on Macrophages

Molecules with the property to induce proliferation of bone marrow cells in liquid cultures, and with colony-stimulating activity, were found on media conditioned (MC) by lung fibroblasts and kidney epithelial cells. These factors presented an apparent mol wt of 70,000 and 22,000 d respectively. Also when MC by epithelial cells from lungs was tested for the induction of proliferation of bone marrow cells a molecule with 22,000 d was detected. These molecules are thought to be CSF because they induce colony formation, and they are also similar in mol wt to two of the already known CSF. In fact the GM-CSF obtained from endotoxic lungs with a large epithelial cell content has a mot wt of 22,000 d, and the CSF-1 produced by a fibroblast cell line had 70,000. When the MC by fibroblast was used to induce bone marrow cells to proliferate, three new molecules with colony-stimulating activity were secreted. These molecules with apparent mol wts of 45,000, 30,000 and 17,000 d were also found in the MC by bone marrow cells when induced to proliferate with MC by epithelial cells. When the 45,000-d molecules was used in induced bone marrow cells to proliferate, once again the 30,000- and the 17,000-d molecules were secreted. Evidence is also provided that the 45,000-d molecule is produced by the monocyte-macrophage cells, and that it can induce Fc receptors or resident and elicited peritoneal macrophages. The possibility that the production of CSF is cell specific is discussed together with two models to explain the way in which these molecules can participate as proliferative (MGI-1) and differentiative (MGI-2) function in normal myeloid cell differentiation. Finally, a new terminology is proposed to classify this family of molecules.