Regulation of the colony-stimulating activity produced by a murine marrow-derived cell line (H-1)

The production of molecular species that stimulate growth of granulocyte or macrophage colonies (GM-CSF) by the fibroblastoid H-1 cell line is unaffected by either native or iron-saturated lactoferrin, although some inhibition is detected with 10 microM prostaglandin E1. The H-1 GM-CSF is able to support the formation of macrophage, neutrophil, and mixed colonies. Feeder layers of H-1 cells are also able to support the development of colony-forming units stimulated by GM-CSF (GM-CFUc) although the number of colonies produced when the optimal H-1 cell concentration is plated (2.5 x 10(3) cells) is only 30% of the number with conditioned medium alone. This inhibitory effect is observed irrespective of the presence of an additional agar layer between the feeder cells and plated bone marrow cells, implying that diffusable substances are involved. Addition of indomethacin (10 microM) to feeder layers derived from 2.5 x 10(3) H-1 cells increases the number of GM-CFUc detected to 50% of that seen with conditioned medium alone. This result suggests that released prostaglandin may be responsible for some, but not all, of the observed inhibition of colony formation. In the presence of the H-1 feeder layers, only macrophage colonies are detected and hence it appears that the H-1 cells produce, in addition to prostaglandin, a diffusible inhibitory substance that preferentially inhibits granulopoiesis.