Stimulating spectrum of human recombinant multi-CSF (IL-3) on human marrow
precursors: importance of accessory cells
FJ Bot, L Dorssers, G Wagemaker and B Lowenberg
Dr Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Recently, human multi-CSF was obtained by molecular cloning. In the present
study, the effects of multi-CSF in vitro were investigated by comparative
culture of whole bone marrow or progenitor cells obtained by sorting the
cell fraction that binds the monoclonal antibody (MoAb) B13C5 (CD 34).
Multi-CSF stimulated erythroid (BFU-E), multipotential (CFU-GEMM) and
eosinophil (CFU-Eo) colonies in cultures of the progenitor cell enriched
fraction, whereas (besides BFU-E, CFU-GEMM, and CFU-Eo) granulocyte
(CFU-G), granulocyte-macrophage (CFU-GM), and macrophage (CFU-M)
colony-forming cells also were stimulated by multi- CSF when unfractionated
bone marrow was cultured. Reconstitution of the progenitor cell fraction
(B13C5 positive) with the B13C5-negative population restored the broad
spectrum of progenitor cell stimulation. This suggested that accessory
cells are required for expression of the full spectrum of progenitor cell
stimulation by multi-CSF. Subsequently, specific marrow cell populations,
including T lymphocytes, granulocytic cells, and monocytes, were prepared
by using selected MoAbs in complement-mediated lysis or cell sorting, added
to cultures of hematopoietic progenitors and tested for accessory cell
function. The results demonstrate that small numbers of monocytes permit
the stimulation of CFU-G, CFU-GM, and CFU-M by multi-CSF. These
monocyte-dependent stimulating effects on CFU-G, CFU-GM, and CFU-M could
also be achieved by adding recombinant GM-CSF as a substitute for monocytes
to the cultures. Therefore, multi-CSF most likely has direct stimulative
effects on BFU-E, CFU-GEMM, and CFU-Eo and indirect effects on CFU-G,
CFU-GM, and CFU-M in the presence of monocytes.
Volume 71,
Issue 6,
pp. 1609-1614,
06/01/1988
Copyright © 1988 by The American Society of Hematology
