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Binding of membrane-anchored macrophage colony-stimulating factor (M- CSF)
to its receptor mediates specific adhesion between stromal cells and M-CSF
receptor-bearing hematopoietic cells
N Uemura, K Ozawa, K Takahashi, A Tojo, K Tani, K Harigaya, S Suzu, K Motoyoshi, H Matsuda and H Yagita
Department of Hematology-Oncology, University of Tokyo, Japan.
To explore the biologic significance of the membrane-anchored form of
macrophage colony-stimulating factor (M-CSF), we examined whether
interaction between membrane-bound M-CSF and its receptor mediates
intercellular adhesion as well as cell proliferation and differentiation.
Human M-CSF receptors were expressed on a murine interleukin-2
(IL-3)-dependent cell line, FDC-P2, by DNA transfection with the c-fms gene
(FDC-P2-MCSFR). A human bone marrow-derived stromal cell line, KM102, was
used in the cell adhesion assay. The expression of membrane-bound M-CSF on
KM102 cells was demonstrated by flow cytometry and immunoblot analysis.
After the incubation of parent and transformed FDC-P2 cells on confluent
KM102 cells, nonadherent cells were removed and the cells attached to KM102
cells were examined microscopically. Almost all parent FDC-P2 cells were
nonadherent, whereas a significant number of FDC-P2-MCSFR cells bound to
KM102 cells. The addition of anti-M-CSF or anti-M-CSF receptor neutralizing
antibodies dose-dependently inhibited the binding of [3H]-thymidine-
labeled FDC-P2-MCSFR cells to KM102 cells. An excess amount of M-CSF also
inhibited the binding. On the other hand, the addition of antibodies
against some representative adhesion molecules (vitronectin receptor,
Pgp-1/CD44, and VLA-4) did not inhibit the adhesion between FDC-P2-MCSFR
cells and KM102 cells. These results support the idea that
membrane-anchored M-CSF and its receptor may function as mediators of
cell-cell adhesion.
Volume 82,
Issue 9,
pp. 2634-2640,
11/01/1993
Copyright © 1993 by The American Society of Hematology

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