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 colon y-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 (M emCSF-1). FDCP-Mix cells with high CSF-1R expression (NAF21 cells) were pla ced on stromal MS-5 cells or STO fibroblasts expressing MemCSF-1 (2M-1 cell s and STO-M2 cells, respectively), in absence of IL-3, NAF21 cells bound si gnificantly to 2M-1 cells as compared to control FDCP-Mix cells. Adhesion o f NAF21 cells was inhibited by anti-huCSF-1 antibodies, as well as anti-huC SF-1R antibodies. Interestingly, NAF21 cells proliferated on both 2M-1 and STO-M2 cells but with very different kinetics. Moreover, NAF21 cell prolife ration was also supported by glutaraldehyde-fixed 2M-1 cells or highly conc entrated MS-5 cell culture supernatant, but not by CSF-1 coated on culture dishes, These results strongly suggest that MemCSF-1/CSF-1R interaction med iates a specific adhesion of NAF21 cells to stromal cells and allows stimul ation 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.