Synergism between hemopoietic growth factors (HGFs) detected by their effects on cells bearing receptors for a lineage specific HGF: Assay of hemopoietin‐1

Abstract

The preceding paper describes a new approach to the detection and assay of growth factors for developmentally early multipotent hemopoietic cells (Bartelmez et al., J. Cell. Physiol., 1985). This approach, involving measurement of the increase in the number of receptors for the mononuclear phagocyte specific hemopoietic growth factor (HGF), colony stimulating factor-1 (CSF-1), in cultures of developmentally early murine cells incubated with putative HGFs, has been used to define and assay hemopoietin-1. Hemopoietin-1 (Mr approximately 20,000) is found in the medium derived from serum-free cultures of cells of the human urinary bladder carcinoma line 5637. In contrast to both hemopoietin-2 and CSF-1, which also stimulate an increase in CSF-1 receptor numbers in cultures of developmentally early hemopoietic cells, hemopoietin-1 alone has no detectable effect. However, hemopoietin-1 exhibits dramatic synergism with CSF-1. In the presence of CSF-1, hemopoietin-1 stimulates the proliferation of developmentally earlier cells than those that respond to either CSF-1 alone or hemopoietin-2 alone or their combination. These cells proliferate for at least 3 days with no alteration of the average CSF-1 receptor density. However, by 5 days of incubation, the progeny of developmentally early hemopoietic cells that have proliferated in response to hemopoietin-1 + CSF-1 exhibit an approximately tenfold increase in the average CSF-1 receptor density per cell, which immediately precedes their differentiation to adherent mononuclear phagocytes. As hemopoietin-1 does not possess colony stimulating or burst promoting activities for murine bone marrow cells, but acts on multipotent hemopoietic cells, the analysis of the mechanism of its synergistic effects with HGFs such as CSF-1 are of special relevance to the regulation of early events in hemopoiesis.

CSF-1 Receptor Signaling in Myeloid Cells

“…macrophage) ( Fig. 1D) (Tushinski et al 1982;Bartelmez and Stanley 1985;Bartelmez et al 1989). Low, HSCequivalent levels of expression of Csf1r mRNA are found on common myeloid (CMP) and common lymphoid (CLP) progenitor cells (Tagoh et al 2002(Tagoh et al , 2004.…”

Incomplete restoration of colony-stimulating factor 1 (CSF-1) function in CSF-1–deficient Csf1op/Csf1op mice by transgenic expression of cell surface CSF-1

“…75,76 In addition, we and others have shown that early hematopoietic progenitor cells express the CSF-1R, [77][78][79] suggesting a role of CSF-1 in early hematopoiesis. TgCS was not able to fully reconstitute the hematopoiesis in the Csf1 op /Csf1 op ; TgCS/ϩ mice.…”

Expression of the human c-fms proto-oncogene product (colony-stimulating factor-1 receptor) on peripheral blood mononuclear cells and choriocarcinoma cell lines.

“…Cells of this lineage (including determined precursors, monoblasts, promonocytes, monocytes, and macrophages) express a single class of high affinity receptors for CSF-1 (2)(3)(4). Although the CSF-1 receptor is expressed by less mature bone marrow progenitors, the number of receptors per cell increases about 10-fold as the cells become committed to the mononuclear phagocyte lineage (5). Thus, circulating peripheral blood monocytes express relatively high numbers of CSF-I receptors, and the populations of CSF-l-binding cells in spleen, lymph nodes, and inflammatory exudates correspond in their number and morphology to macrophages (2,6).…”