The effects of interleukin 3 (IL-3) on cells responsive to macrophage colony-stimulating factor (CSF-1) in liquid murine bone marrow culture.

We have examined variation between inbred mouse strains in the proliferative response of bone marrow cells in liquid culture to macrophage colony-stimulating factor (CSF-1) and interleukin 3 (IL-3). In all mouse strains, thymidine incorporation was stimulated by CSF-1 and, after an initial lag period, it reached a peak on day 5. In contrast, two mouse strains, A/J and Balb c, had much lower proliferative responses to IL-3 than did the other strains. In A/J there was no increase in thymidine incorporation above the initial baseline, although the fall in incorporation seen in the absence of any added growth factor was prevented. IL-3 also prevented the loss of CSF-1 responsiveness observed when A/J bone marrow cells were incubated in medium alone. The lag phase in the response to CSF-1 was progressively abolished following IL-3 pre-treatment. Thus, the data with A/J mice separate two distinct activities of IL-3 and show that proliferation is not required for the synergistic effect exerted by IL-3 on CSF-1-stimulated macrophage generation from bone marrow. In strains in which IL-3 alone was able to stimulate proliferation, its action was not additive with that of CSF-1, and addition of both factors together did not overcome the lag phase. This suggests that the two factors act on the same cell population, and that the known synergistic effect of IL-3 on macrophage colony formation in soft agar does not result from an increase in the initial rate of proliferation. The possibility that the combination of factors might alter the duration of the growth response in vivo is discussed.