Role for monocyte macrophage derived colony stimulating factor and prostaglandin E in the positive and negative feedback control of myeloid stem cell proliferation

J. I. Kurland, H. E. Broxmeyer, L. M. Pelus, R. S. Bockman, M. A. Moore

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Murine peritoneal macrophages and human peripheral blood monocytes stimulated the proliferation in vitro of committed myeloid stem cells (CFU-C) by the elaboration of colony-stimulating factors (CSF). High numbers of monocyte-macrophages possessed little stimulating activity and were markedly suppressive due to the accumulation of a dialyzable, non-species-specific inhibitor of CFU-C proliferation. This inhibitory principle was identified as prostaglandin E (PGE) by means of a sensitive radioimmunoassay, and the levels of PGE correlated inversely with myeloid colony incidence. Suppression of PGE synthesis by indomethacin markedly increased the number and size of myeloid colonies stimulated by monocytes and macrophages and permitted a more accurate estimate of CFU-C incidence. Indomethacin had no direct effect on CFU-C in the absence of a biosynthetic source of PGE and did not influence CSF production occurring in the absence of prostaglandin synthesis. Dose-dependent stimulation of PGE synthesis by macrophages in response to increasing concentrations of CSF was concomitantly associated with progressive CFU-C inhibitory activity. Conversely, monocyte-macrophage PGE synthesis was significantly reduced following exposure to an extract of human granulocytes that decreased CSF production. These studies indicate a unique regulatory function of the monocyte and macrophage in the positive and negative feedback control of committed myeloid stem cell proliferation. The balance between CSF and PGE, factors with mutually opposing actions, is ultimately determined by an afferent feedback mechanism operating via the intrinsic modulation of macrophage PGE synthesis in response to local elevations in CSF concentrations.

Original languageEnglish (US)
Pages (from-to)388-407
Number of pages20
Issue number2
StatePublished - Dec 1 1978


ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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