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KB Leslie, HJ Ziltener and JW Schrader
Biomedical Research Centre, Vancouver, British Columbia, Canada.
WEHI-274.3 is a cell line isolated from an in vivo-derived, murine
myelomonocytic leukemia. Although the survival and growth of WEHI-274.3
cells in vitro is absolutely dependent on the addition of exogenous growth
factors such as interleukin-3 (IL-3), granulocyte-macrophage
colony-stimulating factor (GM-CSF), or colony-stimulating factor-1, when
injected into syngeneic mice the cell line is tumorigenic. Sera from normal
mice contain low levels of an activity that sustains survival of WEHI-274.3
but does not stimulate growth. In contrast, sera from mice bearing the
WEHI-274.3 leukemia contained levels of CSF-1 and GM-CSF that stimulated
the growth of WEHI-274.3 cells. Supernatants of cultures of WEHI-274.3
cells contained an activity that stimulated 3T3 fibroblasts to release an
activity that stimulated the growth of the WEHI-274.3 cells. The
3T3-stimulatory activity released by the WEHI- 274.3 cells was neutralized
completely with an antiserum specific for murine IL-1 alpha, but not with
antiserum specific for IL-1 beta. Moreover, WEHI-274.3 cells both in vitro
and in vivo contained high levels of IL-1 alpha and IL-1 beta mRNAs. The
leukemia-stimulatory activity released by the 3T3 cells was neutralized by
an antiserum specific for GM-CSF. We postulate that the IL-1 alpha
constitutively released by the WEHI-274.3 cells stimulates the production
of GM-CSF from host cells such as fibroblasts or endothelial cells. A
similar paracrine mechanism of growth stimulation may occur in acute
myeloid leukemias in humans.
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| Copyright © 1991 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||