The regulation of mononuclear phagocyte entry into S phase by the colony stimulating factor CSF-1.
CSF-1 is a hemopoietic growth factor that specifically regulates the survival, proliferation, and differentiation of mononuclear phagocytic cells. Populations of adherent bone marrow-derived macrophages (BMM) devoid of CSF-1 producing cells were used to study regulation by CSF-1 of macrophage entry into S phase. More than 95% of BMM possess the CSF-1 receptor. It was shown that 93-98% of BMM are cycling (S phase 8-9 hr, doubling time 24-28 hr) when cultured in the presence of CSF-1. BMM incubated with 15% FCS in the absence of CSF-1 or in the presence of CSF-1 concentrations inducing survival without proliferation enter a quiescent state. This state is characterized by a reduction in the synthesis of DNA (98%), total protein (35%), ribosomal protein (76%), and histone (96%) compared with the synthetic rate of these components in exponentially growing cells. Addition of CSF-1 to BMM rendered quiescent by removal of CSF-1 stimulated entry into S phase with a lag period of approximately 12 h. This lag period is reduced to 8 hr in BMM made quiescent at concentrations of CSF-1 inducing survival without proliferation, an effect which may be related to the expected higher protein content of these cells (Tushinski and Stanley, J. Cell. Physiol., 116:67-75). Neutralization of CSF-1 by antibody at different times during the lag period indicates that CSF-1 is required for almost the entire lag period for the entry of any cells into S phase. In BMM rendered quiescent by removal of both serum and CSF-1, purified CSF-1 without serum stimulated entry of cells into S phase, whereas serum alone was ineffective. The results are consistent with a primary regulatory role of CSF-1 in mononuclear phagocyte proliferation, survival, and function.
D000818:Animals; D001854:Bone Marrow Cells; D002453:Cell Cycle; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000302:isolation & purification / Q000494:pharmacology / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis; D006657:Histones / Q000096:biosynthesis; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D012157:Mononuclear Phagocyte System / Q000166:cytology*; D012269:Ribosomal Proteins / Q000096:biosynthesis
D003115:Colony-Stimulating Factors; D006657:Histones; D012269:Ribosomal Proteins; D004247:DNA