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P Furmanski and CS Johnson
Laboratory of Cell Biology, AMC Cancer Research Center, Denver, CO.
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-1
alpha (IL-1 alpha). The in vivo erythroid suppressive effects of
macrophages, macrophage SN, and IL-1 alpha were reversed by simultaneous
treatment with EPO. IL-1 alpha itself had no effect on CFU- E colony
formation in vitro. Pretreatment of animals with antibodies to murine tumor
necrosis factor-alpha (TNF-alpha) completely abrogated the suppression of
CFU-E by macrophages, macrophage SN, or human recombinant IL-1 alpha. These
results suggest that macrophages regulate erythropoiesis by production of
IL-1 alpha, which in turn mediates its in vivo suppressive effects on CFU-E
through TNF.
This article has been cited by other articles:
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| Copyright © 1990 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
