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, Hal Broxmeyer, Louis Pelus, R. S. Bockman, M. A. Moore

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

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
JournalBlood
Volume52
Issue number2
StatePublished - 1978
Externally publishedYes

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Myeloid Progenitor Cells
Colony-Stimulating Factors
Macrophage Colony-Stimulating Factor
Macrophages
Cell proliferation
Prostaglandins E
Stem cells
Feedback control
Monocytes
Cell Proliferation
Feedback
Indomethacin
Incidence
Peritoneal Macrophages
Granulocyte Colony-Stimulating Factor
Prostaglandins
Radioimmunoassay
Blood
Modulation

ASJC Scopus subject areas

  • Hematology

Cite this

Role for monocyte macrophage derived colony stimulating factor and prostaglandin E in the positive and negative feedback control of myeloid stem cell proliferation. / Kurland, J. I.; Broxmeyer, Hal; Pelus, Louis; Bockman, R. S.; Moore, M. A.

In: Blood, Vol. 52, No. 2, 1978, p. 388-407.

Research output: Contribution to journalArticle

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AU - Kurland, J. I.

AU - Broxmeyer, Hal

AU - Pelus, Louis

AU - Bockman, R. S.

AU - Moore, M. A.

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N2 - 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.

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