Murine Leukemia Viruses: Induction of Macrophage Production of Granulocyte-Macrophage Colony-Stimulating Factor In Vitro23

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Abstract
Infection in vitro of freshly explanted N:NIH(S) mouse bone marrow with ecotropic murine leukemia viruses produced an increase over control uninfected cultures in the 50 or more cell granulocyte-macrophage (GM) colonies and 10–49 cell clusters detected after 7 days of incubation in 0.3% agar at 37° C and 7% CO2. This effect was observed only at plating densities above 5.0×104 cells/ml and was not observed with macrophage-depleted populations of colony-forming units of GM progenitor cells (GM-CFUc) purified by isopyknic density gradient centrifugation of nonadherent cells harvested from long-term bone marrow cultures. Fewer virus-infected, compared to uninfected, peritoneal exudate macrophages were required to stimulate the same number of GM colonies and clusters in a given number of purified GM-CFUc. In contrast, murine leukemia virus infection of T-lymphocytes or NIH/3T3 embryo fibroblasts did not stimulate release of GM-CFUc colony-stimulating factor (CSF). Single cell suspensions of virus-infected freshly explanted whole bone marrow grown in CSF concentrated from L929 or WEHI-3 cell-conditioned medium produced more GM-CFUc colonies and GM clusters/1 ×105 cells compared to single cell suspensions of uninfected marrow. This phenomenon suggests that the colony-forming cells responding to CSF from virus-infected marrow may have been different from those responding to L929 or WEHI-3 cell CSF. The data indicate that increased granulopoiesis observed following retrovirus infection in vivo or in long-term marrow cultures was attributable in part to virus stimulation of production of CSF by adherent marrow stromal cells including macrophages.