Role of the membrane form of human colony-stimulating factor-1 (CSF-1) in proliferation of multipotent hematopoietic FDCP-mix cells expressing human CSF-1 receptor.
Because IL-3-dependent multipotential FDCP-Mix cells expressing human colony-stimulating factor-1 (CSF-1) receptor did not proliferate in response to soluble CSF-1, we investigated whether their proliferation would be induced in co-culture with adherent cells expressing the membrane form of CSF-1 (MemCSF-1). FDCP-Mix cells with high CSF-1R expression (NAF21 cells) were placed on stromal MS-5 cells or STO fibroblasts expressing MemCSF-1 (2M-1 cells and STO-M2 cells, respectively), in absence of IL-3. NAF21 cells bound significantly to 2M-1 cells as compared to control FDCP-Mix cells. Adhesion of NAF21 cells was inhibited by anti-huCSF-1 antibodies, as well as anti-huCSF-1R antibodies. Interestingly, NAF21 cells proliferated on both 2M-1 and STO-M2 cells but with very different kinetics. Moreover, NAF21 cell proliferation was also supported by glutaraldehyde-fixed 2M-1 cells or highly concentrated MS-5 cell culture supernatant, but not by CSF-1 coated on culture dishes. These results strongly suggest that MemCSF-1/CSF-1R interaction mediates a specific adhesion of NAF21 cells to stromal cells and allows stimulation of hematopoietic cells by stromal cell-derived factors expressed in a membrane-bound form or concentrated within the extracellular matrix. Thus, cytokine receptors deficient in mitogenic signalling may nevertheless have a regulatory role in hematopoietic progenitor cell proliferation by acting as adhesion molecules.
Tsuboi
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I
Centre de Génétique Moléculaire et Cellulaire, UMR CNRS 5534, Université Claude Bernard, Villeurbanne, France.
Revol
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V
Blanchet
J P
JP
Mouchiroud
G
G
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D018920:Coculture Techniques; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D016173:Macrophage Colony-Stimulating Factor