Macrophage control of normal and leukemic erythropoiesis: Identification of the macrophage-derived erythroid suppressing activity as interleukin-1 and the mediator of its in vivo action as tumor necrosis factor

P. Furmanski, C. S. Johnson

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44 Scopus citations

Abstract

Macrophages have been shown to directly influence the growth and development of mature erythroid progenitors (CFU-E) in normal and erythroleukemic mice. We examined the mechanism by which macrophages mediate their effect on in vivo erythropoiesis. As reported for whole macrophages, serum-free supernatants (SN) from normal resident peritoneal macrophages suppressed in vivo normal and conventional Friend virus (CFV)-infected CFU-E and caused clinical regression of CFV-induced leukemia in mice. Macrophage SN had no effect on the erythropoietin (EPO)-independent CFU-E characteristic of infection with the polycythemia-inducing strain of Friend virus (FVP), or progression of FVP leukemia. Using biochemical, immunologic, and functional assays, the erythrosuppressive factor in macrophage SN was identified as interleukin-1α (IL-1α). The in vivo erythroid suppressive effects of macrophages, macrophage SN, and IL-1α were reversed by simultaneous treatment with EPO. IL-1α itself had no effect on CFU-E colony formation in vitro. Pretreatment of animals with antibodies to murine tumor necrosis factor-α (TNF-α) completely abrogated the suppression of CFU-E by macrophages, macrophage SN, or human recombinant IL-1α. These results suggest that macrophages regulate erythropoiesis by production of IL-1α, which in turn mediates its in vivo suppressive effects on CFU-E through TNF.

Original languageEnglish (US)
Pages (from-to)2328-2334
Number of pages7
JournalBlood
Volume75
Issue number12
DOIs
StatePublished - 1990
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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