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M Koehler, R Goorha, GR Kitchingman, GD Ayers and J Mirro
Department of Hematology-Oncology, St Jude Children's Research Hospital,
Memphis, TN.
A monoclonal antibody (MoAb) recognizes a novel 52-Kd cell protein (MKW)
that is expressed on cells of the normal myelocytic and monocytic lineage,
a subset of B cells, and the U937 cell line. Using the U937 cell line as a
model, the MoAb (anti-MKW) was examined for its ability to inhibit the
effects of differentiation-inducing factors. In the U937 cell line,
recombinant human granulocyte-macrophage colony-stimulating factor
(rhGM-CSF) inhibits cell proliferation, 12-O-
tetradecanoylphorbol-13-acetate (TPA) inhibits proliferation and induces
the early differentiation antigen CD11b, and vitamin D3 inhibits
proliferation and induces both CD11b and the late differentiation antigen
CD14. The antiproliferative and differentiation effects of rhGM-CSF and
vitamin D3 on U937 cells were inhibited by the anti-MKW MoAb. Similar
effects were seen when anti-MKW antibody was added 30 minutes before or 2
hours after rhGM-CSF or vitamin D3, suggesting that its effects are not
mediated by blocking or binding to the receptors for these growth factors.
The anti-MKW MoAb had no effect on TPA-induced differentiation in U937
cells, indicating that TPA exerts its effects through a pathway different
from rhGM-CSF and vitamin D3. These results suggest that the MKW antigen is
important in controlling the proliferation and differentiation of monocytic
cells.
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