Regulation of human monocyte DNA synthesis by colony-stimulating factors, cytokines, and cyclic adenosine monophosphate

DL Cheung and JA Hamilton


It is reported in this study that a subpopulation of highly purified human peripheral blood human monocytes can proliferate in response to colony-stimulating factor-1 (CSF-1), granulocyte-macrophage colony- stimulating factor (GM-CSF), and interleukin-3 (IL-3). Both GM-CSF and IL-3 synergized with CSF-1 for the induction of DNA synthesis. Given the DNA synthesis levels attained, we were able to test the effects of certain cytokines and cyclic adenosine monophosphate (cAMP)-elevating agents, which have been shown to modulate in vitro human myelopoiesis and murine macrophage proliferation. The cytokines, interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF- alpha), as well as cAMP-elevating agents, 8-bromoadenosine 3′:5′-cyclic monophosphate (8BrcAMP), cholera toxin (CT), and prostaglandin E2 (PGE2), suppressed the monocyte DNA synthesis due to CSF-1. These results parallel those reported with human bone marrow progenitors, as well as murine macrophage populations. The cycling human monocyte population could provide a model cell type to understand the molecular events controlling human myelopoiesis.