Influence of Cytokine Stimulation (Granulocyte Macrophage-Colony Stimulating Factor, lnterleukin-3 and Transforming Growth Factor-Beta-1) on Adhesion Molecule Expression in Normal Human Bone Marrow Fibroblasts

1995 ◽  
Vol 94 (4) ◽  
pp. 173-181 ◽  
Author(s):  
B. Schmitz ◽  
I.A. Park ◽  
R. Kaufmann ◽  
J. Thiele ◽  
R. Fischer
Blood ◽  
1995 ◽  
Vol 86 (6) ◽  
pp. 2130-2136 ◽  
Author(s):  
CM Chang ◽  
A Limanni ◽  
WH Baker ◽  
ME Dobson ◽  
JF Kalinich ◽  
...  

The effects of a myeloablative sublethal 775 cGy 60C gamma radiation exposure on endogenous bone marrow (BM) and splenic granulocyte- macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-beta (TGF-beta) mRNA levels were assayed in B6D2F1 female mice. BM and spleen were harvested from normal mice and irradiated mice on days 2, 4, 7, 10, and 14 after exposure. Cytokine mRNA levels were determined using reverse transcription-polymerase chain reaction. After irradiation, GM-CSF mRNA levels were significantly increased in the BM from days 2 to 10 and in the spleen from days 4 to 10. However, when BM and splenic GM-CSF protein levels were measured using Western dot blot, no increased protein levels were detected. Serum GM-CSF levels were likewise unchanged. Radiation exposure did not affect BM or splenic TGF- beta mRNA levels and this cytokine is known to be produced by cell populations similar to those that produce GM-CSF. These data suggest that radiation injury to hemopoietic tissues results in differential effects on GM-CSF and TGF-beta mRNA levels and that, in the case of GM- CSF, increased mRNA levels are not matched by increased protein production.


Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2239-2247 ◽  
Author(s):  
SE Jacobsen ◽  
JR Keller ◽  
FW Ruscetti ◽  
P Kondaiah ◽  
AB Roberts ◽  
...  

Transforming growth factor-beta (TGF-beta) has potent antiproliferative effects on human hematopoietic progenitor cells. We report here that TGF-beta 1 and -beta 2 also exert bimodal dose-dependent stimulation of granulocyte-macrophage colony-stimulating factor (CSF) and granulocyte- CSF-induced day 7 granulocyte-macrophage colony-forming units. This increase in colony formation was restricted to low doses (0.01 to 1.0 ng/mL) of TGF-beta 1 and was due to increased granulopoiesis, showing that TGF-beta can affect the differentiation as well as the proliferation of hematopoietic progenitors. Furthermore, TGF-beta 3 was found to be a more potent inhibitor of hematopoietic progenitor cells than TGF-beta 1 and -beta 2. In contrast to the bidirectional proliferative effects of TGF-beta 1 and -beta 2, the effects of TGF- beta 3 on human hematopoiesis were only inhibitory, showing for the first time that TGF-beta isoforms differ not only in potencies but also with regard to the nature of the response they elicit.


Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 758-765 ◽  
Author(s):  
G Kannourakis ◽  
GR Johnson

Abstract Normal human bone marrow mononuclear cells were fractionated by differential adherence, immunomagnetic separation, and fluorescence- activated cell sorting (FACS). The resultant fractionated cells were cultured in semisolid medium to monitor the presence of BFU-E, Mix-CFC, and nonerythroid CFC. Two populations of cells were recovered on the basis of binding by the monoclonal antibody (MoAb) RFB-1. One of these populations contained BFU-E that were stimulated only by erythropoietin (Epo), whereas the second population contained BFU-E responsive to Epo, Epo and recombinant human granulocyte-macrophage colony-stimulating factor (rHGM-CSF), or Epo and human placental-conditioned medium (HPCM). Prior enrichment of clonogenic cells by removal of adherent and Leu-M3+ve, Leu-4+ve, Leu-7+ve, B1+ve, WEMG1+ve, and Glycophorin A+ve cells, followed by FACS fractionation on the basis of RFB-1 binding, consistently resulted in recoveries of BFU-E, Mix-CFC, and nonerythroid CFC of greater than 100% (up to 800%). These procedures also resulted in enrichment of up to 200-fold and frequencies of 1:6 for BFU-E, 1:5 for CFC, and 1:130 for Mix-CFC.


Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 758-765 ◽  
Author(s):  
G Kannourakis ◽  
GR Johnson

Normal human bone marrow mononuclear cells were fractionated by differential adherence, immunomagnetic separation, and fluorescence- activated cell sorting (FACS). The resultant fractionated cells were cultured in semisolid medium to monitor the presence of BFU-E, Mix-CFC, and nonerythroid CFC. Two populations of cells were recovered on the basis of binding by the monoclonal antibody (MoAb) RFB-1. One of these populations contained BFU-E that were stimulated only by erythropoietin (Epo), whereas the second population contained BFU-E responsive to Epo, Epo and recombinant human granulocyte-macrophage colony-stimulating factor (rHGM-CSF), or Epo and human placental-conditioned medium (HPCM). Prior enrichment of clonogenic cells by removal of adherent and Leu-M3+ve, Leu-4+ve, Leu-7+ve, B1+ve, WEMG1+ve, and Glycophorin A+ve cells, followed by FACS fractionation on the basis of RFB-1 binding, consistently resulted in recoveries of BFU-E, Mix-CFC, and nonerythroid CFC of greater than 100% (up to 800%). These procedures also resulted in enrichment of up to 200-fold and frequencies of 1:6 for BFU-E, 1:5 for CFC, and 1:130 for Mix-CFC.


Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2239-2247 ◽  
Author(s):  
SE Jacobsen ◽  
JR Keller ◽  
FW Ruscetti ◽  
P Kondaiah ◽  
AB Roberts ◽  
...  

Abstract Transforming growth factor-beta (TGF-beta) has potent antiproliferative effects on human hematopoietic progenitor cells. We report here that TGF-beta 1 and -beta 2 also exert bimodal dose-dependent stimulation of granulocyte-macrophage colony-stimulating factor (CSF) and granulocyte- CSF-induced day 7 granulocyte-macrophage colony-forming units. This increase in colony formation was restricted to low doses (0.01 to 1.0 ng/mL) of TGF-beta 1 and was due to increased granulopoiesis, showing that TGF-beta can affect the differentiation as well as the proliferation of hematopoietic progenitors. Furthermore, TGF-beta 3 was found to be a more potent inhibitor of hematopoietic progenitor cells than TGF-beta 1 and -beta 2. In contrast to the bidirectional proliferative effects of TGF-beta 1 and -beta 2, the effects of TGF- beta 3 on human hematopoiesis were only inhibitory, showing for the first time that TGF-beta isoforms differ not only in potencies but also with regard to the nature of the response they elicit.


1997 ◽  
Vol 8 (3) ◽  
pp. 469-480 ◽  
Author(s):  
M Muramatsu ◽  
J Yan ◽  
K Eto ◽  
T Tomoda ◽  
R Yamada ◽  
...  

Receptor-type serine/threonine kinases (RSKs) have been organized into two distinct classes known as types I and II on the basis of sequence similarity. However, experiments have shown ligand specificities in the two classes and as a result type I and type II receptors can often bind to a common ligand. The transforming growth factor-beta- (TGF-beta) specific receptors represent such a case, where both type I and II receptors (T beta RI and T beta RII) are observed. Of additional interest is the observation that heteromeric associations of type I and II receptors can also enable signaling. To further elucidate the function of various RSKs, the extracellular domains of both alpha and beta chains from human granulocyte-macrophage colony-stimulating factor receptors were linked to transmembrane cytoplasmic domains of RSKs. Chimeric receptors of human granulocyte-macrophage receptor (hGMR) alpha with T beta RI and hGMR beta with T beta RII were expressed in murine pre-B cell-derived Ba/F3 cells. These chimeras formed heteromeric complexes, transmitted TGF-beta signals, and were down-modulated in response to human granulocyte-macrophage colony-stimulating factor. However, experiments utilizing these chimeric receptors in different combinations revealed that only heteromeric associations of transmembrane cytoplasmic domains mediated signaling and down-modulation. Chimeric receptors with transmembrane cytoplasmic domains of activin receptor type II and bone morphogenetic protein receptor type II also provided signals in conjunction with chimeric T beta RI. As a result, these type II receptors may share a common potential to signal via T beta RI. hGMR-RSK chimeric receptors may be useful tools for the identification and characterization of the divergent signals mediated by individual RSKs.


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