Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy

Robert J. Tushinski, Ivan T. Oliver, Larry J. Guilbert, P. Wendy Tynan, Jonathan R. Warner, E. Richard Stanley

Research output: Contribution to journalArticle

446 Citations (Scopus)

Abstract

CSF-1 is a hemopoietic growth factor that specifically causes the proliferation and differentiation of mononuclear phagocytic cells. Receptors for CSF-1 occur exclusively on cells of the mononuclear phagocytic series (precursor → monoblast → promonocyte → monocyte → macrophage). Studies of the actions of CSF-1 on freshly explanted macrophages have been complicated by contamination of the primary cell isolates with CSF-1-producing cells and by the heterogeneity of the proliferative responses of individual macrophages. A method is described for the production of a highly purified and homogeneous population of adherent bone marrow-derived macrophages (BMMs) that are devoid of CSF-1-producing cells. The method may also be used to obtain nonadherent precursors of the mononuclear phagocytic series. Studies of CSF-1 action and degradation in cultures of BMMs have revealed several new findings. First, CSF-1 is required for both the survival (without proliferation) and the proliferation of BMMs. Second CSF-1 is degraded by BMMs in a concentration-dependent manner, over the range of concentrations that stimulates both cell survival and proliferation. Third, the rate of CSF-1 degradation is saturable (∼7 × 104 molecules per cell per hour) at CSF-1 concentrations that cause maximum proliferation (∼0.4 nM). Under these conditions, BMMs are greatly enlarged and contain numerous phase-lucent vacuoles. Thus macrophages specifically require CSF-1 for both survival and proliferation, yet selectively and rapidly degrade it. This apparent dichotomy may have important implications for the role of CSF-1 in macrophage homeostasis in vivo.

Original languageEnglish (US)
Pages (from-to)71-81
Number of pages11
JournalCell
Volume28
Issue number1
DOIs
StatePublished - 1982

Fingerprint

Macrophage Colony-Stimulating Factor
Phagocytes
Macrophages
Intercellular Signaling Peptides and Proteins
Bone
Monocyte-Macrophage Precursor Cells
Macrophage Colony-Stimulating Factor Receptors
Cells
Degradation
Vacuoles
Cell culture
Monocytes
Cell Survival
Contamination
Homeostasis
Cell Proliferation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Tushinski, R. J., Oliver, I. T., Guilbert, L. J., Tynan, P. W., Warner, J. R., & Stanley, E. R. (1982). Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. Cell, 28(1), 71-81. https://doi.org/10.1016/0092-8674(82)90376-2

Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. / Tushinski, Robert J.; Oliver, Ivan T.; Guilbert, Larry J.; Tynan, P. Wendy; Warner, Jonathan R.; Stanley, E. Richard.

In: Cell, Vol. 28, No. 1, 1982, p. 71-81.

Research output: Contribution to journalArticle

Tushinski, Robert J. ; Oliver, Ivan T. ; Guilbert, Larry J. ; Tynan, P. Wendy ; Warner, Jonathan R. ; Stanley, E. Richard. / Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. In: Cell. 1982 ; Vol. 28, No. 1. pp. 71-81.
@article{1067498d0e264af3a4f981b592a85b60,
title = "Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy",
abstract = "CSF-1 is a hemopoietic growth factor that specifically causes the proliferation and differentiation of mononuclear phagocytic cells. Receptors for CSF-1 occur exclusively on cells of the mononuclear phagocytic series (precursor → monoblast → promonocyte → monocyte → macrophage). Studies of the actions of CSF-1 on freshly explanted macrophages have been complicated by contamination of the primary cell isolates with CSF-1-producing cells and by the heterogeneity of the proliferative responses of individual macrophages. A method is described for the production of a highly purified and homogeneous population of adherent bone marrow-derived macrophages (BMMs) that are devoid of CSF-1-producing cells. The method may also be used to obtain nonadherent precursors of the mononuclear phagocytic series. Studies of CSF-1 action and degradation in cultures of BMMs have revealed several new findings. First, CSF-1 is required for both the survival (without proliferation) and the proliferation of BMMs. Second CSF-1 is degraded by BMMs in a concentration-dependent manner, over the range of concentrations that stimulates both cell survival and proliferation. Third, the rate of CSF-1 degradation is saturable (∼7 × 104 molecules per cell per hour) at CSF-1 concentrations that cause maximum proliferation (∼0.4 nM). Under these conditions, BMMs are greatly enlarged and contain numerous phase-lucent vacuoles. Thus macrophages specifically require CSF-1 for both survival and proliferation, yet selectively and rapidly degrade it. This apparent dichotomy may have important implications for the role of CSF-1 in macrophage homeostasis in vivo.",
author = "Tushinski, {Robert J.} and Oliver, {Ivan T.} and Guilbert, {Larry J.} and Tynan, {P. Wendy} and Warner, {Jonathan R.} and Stanley, {E. Richard}",
year = "1982",
doi = "10.1016/0092-8674(82)90376-2",
language = "English (US)",
volume = "28",
pages = "71--81",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy

AU - Tushinski, Robert J.

AU - Oliver, Ivan T.

AU - Guilbert, Larry J.

AU - Tynan, P. Wendy

AU - Warner, Jonathan R.

AU - Stanley, E. Richard

PY - 1982

Y1 - 1982

N2 - CSF-1 is a hemopoietic growth factor that specifically causes the proliferation and differentiation of mononuclear phagocytic cells. Receptors for CSF-1 occur exclusively on cells of the mononuclear phagocytic series (precursor → monoblast → promonocyte → monocyte → macrophage). Studies of the actions of CSF-1 on freshly explanted macrophages have been complicated by contamination of the primary cell isolates with CSF-1-producing cells and by the heterogeneity of the proliferative responses of individual macrophages. A method is described for the production of a highly purified and homogeneous population of adherent bone marrow-derived macrophages (BMMs) that are devoid of CSF-1-producing cells. The method may also be used to obtain nonadherent precursors of the mononuclear phagocytic series. Studies of CSF-1 action and degradation in cultures of BMMs have revealed several new findings. First, CSF-1 is required for both the survival (without proliferation) and the proliferation of BMMs. Second CSF-1 is degraded by BMMs in a concentration-dependent manner, over the range of concentrations that stimulates both cell survival and proliferation. Third, the rate of CSF-1 degradation is saturable (∼7 × 104 molecules per cell per hour) at CSF-1 concentrations that cause maximum proliferation (∼0.4 nM). Under these conditions, BMMs are greatly enlarged and contain numerous phase-lucent vacuoles. Thus macrophages specifically require CSF-1 for both survival and proliferation, yet selectively and rapidly degrade it. This apparent dichotomy may have important implications for the role of CSF-1 in macrophage homeostasis in vivo.

AB - CSF-1 is a hemopoietic growth factor that specifically causes the proliferation and differentiation of mononuclear phagocytic cells. Receptors for CSF-1 occur exclusively on cells of the mononuclear phagocytic series (precursor → monoblast → promonocyte → monocyte → macrophage). Studies of the actions of CSF-1 on freshly explanted macrophages have been complicated by contamination of the primary cell isolates with CSF-1-producing cells and by the heterogeneity of the proliferative responses of individual macrophages. A method is described for the production of a highly purified and homogeneous population of adherent bone marrow-derived macrophages (BMMs) that are devoid of CSF-1-producing cells. The method may also be used to obtain nonadherent precursors of the mononuclear phagocytic series. Studies of CSF-1 action and degradation in cultures of BMMs have revealed several new findings. First, CSF-1 is required for both the survival (without proliferation) and the proliferation of BMMs. Second CSF-1 is degraded by BMMs in a concentration-dependent manner, over the range of concentrations that stimulates both cell survival and proliferation. Third, the rate of CSF-1 degradation is saturable (∼7 × 104 molecules per cell per hour) at CSF-1 concentrations that cause maximum proliferation (∼0.4 nM). Under these conditions, BMMs are greatly enlarged and contain numerous phase-lucent vacuoles. Thus macrophages specifically require CSF-1 for both survival and proliferation, yet selectively and rapidly degrade it. This apparent dichotomy may have important implications for the role of CSF-1 in macrophage homeostasis in vivo.

UR - http://www.scopus.com/inward/record.url?scp=0020078038&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020078038&partnerID=8YFLogxK

U2 - 10.1016/0092-8674(82)90376-2

DO - 10.1016/0092-8674(82)90376-2

M3 - Article

VL - 28

SP - 71

EP - 81

JO - Cell

JF - Cell

SN - 0092-8674

IS - 1

ER -