Human erythroid burst-forming units. Growth in vitro is dependent on monocytes, but not T lymphocytes.

196

Monokine-stimulated endothelial cells are known to produce both burst-and colony-stimulating activities, but neither the nature of the monokine nor the hematopoietic growth factor(s) produced is known. We show by mRNA analysis that an immortalized line of human endothelial cells constitutively produce grknulocyte-macrophage colony-stimulating factor. Furthermore, interleukin 1 and tumor necrosis factor induce early passage human umbilical endothelial cells to produce the same growth factor.

“…Monocytes (7)(8)(9)(10) and T-lymphocytes (33,34) have been previously reported as major circulating cell sources of BPA and CSA, whereas fixed "stromal" endothelial cells (4-6, 12, 13) …”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Interleukin 1 induces cultured human endothelial cell production of granulocyte-macrophage colony-stimulating factor.

Sieff¹,

Tsai²,

Faller³

1987

196

“…The mechanism(s) underlying the suppressive effect of IFN on hematopoiesis is not known. In this regard, it is generally accepted that immunocompetent cells, principally T cells and monocyte-macrophages (MO) play an important regulatory role in hematopoietic progenitor cell activity (18)(19)(20)(21). Furthermore, increasing evidence points to IFN as a potent modulator of a variety of cell-mediated immune responses (22,23); IFN have been shown to augment the cytotoxic activities of MO and natural killer cells (8,24).…”

mentioning

confidence: 99%

Suppression of normal human erythropoiesis by gamma interferon in vitro. Role of monocytes and T lymphocytes.

Mamus¹,

Beck-Schroeder²,

Zanjani³

1985

129

Interferons (IFN) have been shown to suppress the proliferation of human erythroid progenitors (erythroid burst-forming units IBFU-EI and colony-forming units [CFU-E]) in vitro. To examine the mechanism(s) underlying this inhibitory activity, the effect of different doses (50-10,000 U) of a highly purified preparation of recombinant DNA producfd human 'y-IFN on erythroid colony formation by normal human bone marrow BFU-E and CFU-E in the presence and absence of monocytes and/or T lymphocytes was studied. The addition of y-IFN to whole marrow caused suppression of BFU-E (6-65%) and CFU-E (31-79%) in a dose-dependent fashion. This inhibition occurred both with the direct addition of y-IFN to the culture plates as well as by the preincubation of marrow cells with y-IFN followed by the washing of the cells; at the highest concentration of y-IFN (10,000 U), near-maximal inhibition of colony formation occurred with as little as 15 min of preexposure (BFU-E, 50%; CFU-E, 81%). Removal of monocytes and/or T lymphocytes before the addition of "y-IFN significantly reduced the inhibitory effects of this lymphokine (BFU-E, -1 to 38%; CFU-E, -8 to 67%). Co-culture of purified autologous monocytes or T cells preexposed to 'y-IFN with monocyte and T cell-depleted marrow cells resulted in highly significant inhibition of erythroid colony formation even when these treated cells comprised <1% of the total nucleated cell populations in culture. The inhibitory action of y-IFN was not prevented or reversed by erythropoietin. These results demonstrate that the inhibitory effects of -y-IFN on erythropoiesis are mediated to a significant degree through accessory cell populations, and suggest that 'y-IFN may represent a useful tool in the study of the role of immunocompetent cells in the regulation of erythropoiesis in vitro.

“…Although the cellular mechanism for LDL suppression is unknown, our approach may be applicable to the study of this phenomenon since serum LDL are known to inhibit a number of lymphocyte responses, including generation of an immune response and lymphoproliferation both in vitro and in vivo (37-49). Because hematopoietic growth-promoting molecules are released from peripheral blood mononuclear cells (25,(50)(51)(52), it is possible that LDL alter interactions among various lymphocyte and/or monocyte populations and other cell types, including hematopoietic progenitor cells and endothelial cells. Such interactions have been reported to be important in the generation of multilineage and granulocyte/macrophage colony-stimulating activities from cultured endothelial cells (53)(54)(55)(56)(57).…”

Section: Discussionmentioning

confidence: 99%

Acetylated lipoproteins impair erythroid growth factor release from endothelial cells.

Dainiak

Warren²,

Kreczko³

et al. 1988

Endothelial cells are a known source of hematopoietic growthenhancing factors, including platelet-derived growth factor (PDGF). In addition, endothelium interacts directly with plasma lipoproteins which have been shown to modulate hematopoiesis. To determine the relationship of these properties, we measured the release of an erythroid growth-enhancing factor from bovine endothelial cells under lipid-loaded and control conditions. Human bone marrow cells cultured under serum-free conditions form more erythroid, granulocyte/macrophage, and mixed hematopoietic colonies when supplemented with endothelial cell-conditioned medium (ECCM) than do controls (P < 0.05). The activity is expressed over a wide range of erythropoietin, lymphocyte-conditioned medium (LCM), recombinant human interleukin-3, and colony-stimulating factor (CSF) concentrations, and is related to ECCM dose. In contrast, enhancing activity in ECCM prepared with 0-400 ,ug/ml acetylated low density lipoproteins (AcLDL) or native LDL is diminished to 0% in a dose-dependent fashion (relative to ECCM from unexposed cells or from cells incubated with very low density lipoproteins, P < 0.05). Upon dilution, medium prepared from cells incubated with LDL shows a rightward shift in the dose-response curve for erythroid colony formation, while that prepared from AcLDL loaded cells demonstrates a downward shift, indicating that the inhibitory activities are kinetically distinct. Delipidation of ECCM prior to addition to marrow culture removes the inhibitory action of native LDL (P < 0.05) but not that of AcLDL (P > 0.10). Immunochemical analysis suggests that the erythropoietic activity in ECCM is unrelated to that of PDGF, recombinant human CSF, and erythroid burst-promoting activity (BPA) present in LCM. This conclusion is supported by Northern blot analysis of endothelial cells using a cDNA probe for the v-sis homologue of the PDGF , chain and by immunoprecipitation of metabolically labeled PDGF. The relative amounts of c-sis transcripts and of secreted PDGF were simi-