In Vitro Development of Bone‐Marrow‐Derived Macrophages Influence of Mouse Genotype on Response to Colony‐Stimulating Factors and Autocrine Interferon Induction

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Abstract
Responsiveness to granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and macrophage CSF (M‐CSF) of bone marrow cells derived from different mouse strains was investigated. There were great variations in proliferation between different strains of inbred mice. Bone marrow cells from mouse strains with a high rate of proliferation in response to GM‐CSF also had a high proliferating capacity to M‐CSF. The response to either CSF did not correlate with a certain H‐2 haplotype. GM‐CSF induced consistently higher proliferation than M‐CSF. Proliferation in response to M‐CSF, but not to GM‐CSF, could be enhanced by the addition of antibodies against interferon (IFN). IFN is the only known inducer of (2′‐5′) oligoadenylate (oligo (A)) synthetase. This enzyme was induced in macrophages grown in the presence of M‐CSF, but not in GM‐CSF promoted cells. Enzyme induction was completely abrogated by simultaneous treatment with anti‐IFNα/β. Infection of macrophages with herpes simplex virus type 1 (HSV) and vesicular stomatitis virus (VSV) revealed that GM‐CSF‐promoted cells were highly susceptible to lytic infection by these viruses. In contrast, virus titres in M‐CSF‐cultured cells were 100‐fold lower. We conclude that, contrary to M‐CSF, GM‐CSF does not induce autocrine IFN during haematopoiesis. As judged from data with BALB/c mice, the sensitivity to the anti‐proliferative effect of the autocrine IFN may be a factor which influences M‐CSF‐promoted proliferation.