Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we show how Rhodamine-123 (Rh-123), as in other hematopoietic populations, can be used to define functionally distinct progenitor cells from human umbilical cord blood (HUCB). CD34+ cells were subdivided into Rh-123high (78.2 +/- 4.5%) and Rh-123low (21.8 +/- 3.6%). While 9.3 +/- 1.6% of the CD34+Rh-123high cells formed colonies in agar, only 0.4 +/- 0.2% of the CD34+Rh-123low population did so. However, the CD34+Rh-123low cells resulted in the greatest expansion of colony-forming cells (CFC) when cultured in liquid medium with different cytokine combinations. When the CD34+Rh-123low cells were cultured for 7 days with stem cell factor (SCF) and erythropoietin (Epo), the CD34+Rh-123low cells resulted in a 94-fold increase in CFC compared with a 2.5-fold increase from the CD34+Rh-123high cells. The combination of SCF and Epo or granulocyte-macrophage colony-stimulating factor (GM-CSF) supported the production and maintenance of CFC from CD34+Rh-123low cells > 28 days compared with only 21 days for the CD34+Rh-123high cells. Coculture of CD34+Rh-123low cells with stromal cell line 11 (SCL11) demonstrated that long-term culture initiating cells (LTCIC) were present within this population, as CFC could be recovered for > 10 weeks compared with < 6 weeks in cocultures with CD34+Rh-123high cells. The duration of maintenance of CFC in liquid culture could be further enhanced by the addition of an antibody (Ab) directed against the binding site of the GM-CSF receptor. The addition of anti-GM-CSF receptor Ab to cultures of CD34+Rh-123high and low cells supplemented with SCF, interleukin-3 (IL-3), and IL-6 resulted in an initial 10-fold decrease in CFC in cultures of both the CD34+Rh-123high and low cells. Although very few CFCs were present by 42 days in liquid cultures of CD34+Rh-123high cells, the number of CFCs in these cultures was significantly increased when anti-GM-CSF receptor Ab was added. Although this effect was also observed in cultures of CD34+Rh-123low cells, it was less dramatic as more CFC persisted even in the absence of Ab. The possible mechanism of this effect is discussed.
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PMID:The effect of cytokines on CD34+ Rh-123high and low progenitor cells from human umbilical cord blood. 752 27

Recently, we have demonstrated that antibodies that block the function of the beta2-integrin leukocyte function-associated antigen-1 (LFA-1) completely abrogate the rapid mobilization of hematopoietic progenitor cells (HPC) with colony-forming and radioprotective capacity induced by interleukin-8 (IL-8) in mice. These findings suggested a direct inhibitory effect of these antibodies on LFA-1-mediated transmigration of stem cells through the bone marrow endothelium. Therefore, we studied the expression and functional role of LFA-1 on murine HPC in vitro and in vivo. In steady state bone marrow +/- 50% of the mononuclear cells (MNC) were LFA-1(neg). Cultures of sorted cells, supplemented with granulocyte colony-stimulating factor (G-CSF)/granulocyte-macrophage colony-stimulating factor (GM-CSF)/IL-1/IL-3/IL-6/stem cell factor (SCF) and erythropoietin (EPO) indicated that the LFA-1(neg) fraction contained the majority of the colony-forming cells (CFCs) (LFA-1(neg) 183 +/- 62/7,500 cells v LFA-1(pos) 29 +/- 17/7,500 cells, P <.001). We found that the radioprotective capacity resided almost exclusively in the LFA-1(neg) cell fraction, the radioprotection rate after transplantation of 10(3), 3 x 10(3), 10(4), and 3 x 10(4) cells being 63%, 90%, 100%, and 100% respectively. Hardly any radioprotection was obtained from LFA-1(pos) cells. Similarly, in cytokine (IL-8 and G-CSF)-mobilized blood, the LFA-1(neg) fraction, which comprised 5% to 10% of the MNC, contained the majority of the colony-forming cells, as well as almost all cells with radioprotective capacity. Subsequently, primitive bone marrow-derived HPC, represented by Wheat-germ-agglutinin (WGA)+/Lineage (Lin)-/Rhodamine (Rho)- sorted cells, were examined. More than 95% of the Rho- cells were LFA-1(neg). Cultures of sorted cells showed that the LFA-1(neg) fraction contained all CFU. Transplantation of 150 Rho- LFA-1(neg) or up to 600 Rho-LFA-1(pos) cells protected 100% and 0% of lethally irradiated recipient mice, respectively. These results show that primitive murine HPC in steady-state bone marrow and of cytokine-mobilized blood do not express LFA-1.
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PMID:Murine hematopoietic progenitor cells with colony-forming or radioprotective capacity lack expression of the beta 2-integrin LFA-1. 986 52