Selective production of interleukin 3 (IL 3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in vitro by murine L3T4 T cells: lack of spontaneous IL 3 and GM-CSF production by Ly-2−/ L3T4− lpr subset

1988 ◽  
Vol 18 (9) ◽  
pp. 1367-1372 ◽  
Author(s):  
Jean-Luc Davignon ◽  
Makoto Kimoto ◽  
Vincent Kindler ◽  
Sylvie De Kossodo ◽  
Pierre Vassalli And ◽  
...  
Keyword(s):  
T Cells ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Csf Production

scholarly journals Dexamethasone and 1,25-dihydroxyvitamin D3, but not cyclosporine A, inhibit production of granulocyte-macrophage colony-stimulating factor in human fibroblasts

Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 1912-1918 ◽  
Author(s):  
A Tobler ◽  
HP Marti ◽  
C Gimmi ◽  
AB Cachelin ◽  
S Saurer ◽  
...  
Keyword(s):  
Human Fibroblasts ◽  
Tnf Alpha ◽  
Colony Stimulating Factor ◽  
Dihydroxyvitamin D3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Csf Production

Abstract Tumor necrosis factor alpha (TNF alpha) stimulates granulocyte- macrophage colony-stimulating factor (GM-CSF) production in human fibroblasts and other mesenchymal cells. However, relatively little is known about agents that downregulate cytokine production in these cells. In the present report we show that dexamethasone (Dexa), a synthetic glucocorticoid, markedly reduced GM-CSF production in TNF alpha-stimulated fibroblasts at both the protein and the RNA levels. CSF activity, GM-CSF protein, and RNA levels, determined by an in vitro colony-forming assay in normal human bone marrow cells, by an enzyme immunoassay, and by Northern blotting assay, were reduced to greater than 90% of control values by Dexa (1 mumol/L). Similarly, 1,25- dihydroxyvitamin D3 [1,25(OH)2D3], a hormone with possible physiologic immunoregulatory significance, reduced GM-CSF expression in a concentration- and time-dependent manner. However, this repression was less pronounced than that of Dexa, and in part due to a decreased proliferative activity. In contrast, cyclosporine A (CsA), another immunosuppressive agent, did not alter GM-CSF expression in TNF alpha- stimulated fibroblasts. Our in vitro studies suggest that by inhibiting GM-CSF production in fibroblasts, glucocorticoids and possibly 1,25(OH)2D3, but not CsA, may attenuate TNF alpha-mediated inflammatory processes and influence the regulation of hematopoiesis.

scholarly journals Enhanced marrow recovery by short preincubation of marrow allografts with human recombinant interleukin-3 and granulocyte-macrophage colony- stimulating factor

Blood ◽  
1992 ◽  
Vol 80 (7) ◽  
pp. 1673-1678 ◽  
Author(s):  
E Naparstek ◽  
Y Hardan ◽  
M Ben-Shahar ◽  
A Nagler ◽  
R Or ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Study Group ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Duration Of Hospitalization ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

We studied an alternative method of using hematopoietic growth factors (HGFs) to enhance hematopoietic recovery in patients undergoing bone marrow transplantation (BMT), by short in vitro preincubation. Twenty consecutive patients with leukemia received T-cell-depleted allografts using Campath-1G. Two thirds of the marrow was infused on the scheduled day of transplant and one third of the marrow following preincubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) on day 4. Engraftment parameters and duration of hospitalization were compared by actuarial analysis to those of 40 historical controls. Patients receiving the incubated boost had significantly faster platelet recovery (P = .017) and shorter hospitalization period (P = .001) when compared with the control subjects. Platelet count reached greater than 25 x 10(9)/L on day 17 (median) in the study group and on day 23 in the controls. The median duration of hospitalization was 20 and 36 days, respectively. In the early posttransplantation follow-up, two of four patients in the study group died as a result of graft rejection, while all 13 deaths in the control group resulted from complications associated with marrow suppression. We suggest that pretransplant in vitro activation of bone marrow cells with IL-3 and GM-CSF may prove to be an efficient method for enhancing marrow recovery after BMT.

scholarly journals Effects of interleukin-3 and granulocyte-macrophage colony-stimulating factor on thrombopoiesis in congenital amegakaryocytic thrombocytopenia

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1691-1698 ◽  
Author(s):  
EC Guinan ◽  
YS Lee ◽  
KD Lopez ◽  
S Kohler ◽  
DH Oette ◽  
...  
Keyword(s):  
Optimal Dose ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Significant Toxicity ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Amegakaryocytic thrombocytopenia (AMT) is a rare and often fatal disorder of infancy and childhood presenting with isolated thrombocytopenia that progresses to marrow failure. The defect in thrombopoiesis is not well understood nor is the etiology of the progressive marrow failure. No standard modality of treatment exists. Here, we evaluated the capacity of marrow cells isolated from five patients with AMT and progressive marrow failure to generate megakaryocyte progenitor cells (CFU-MK). These in vitro studies demonstrated assayable numbers of CFU-MK from all patient bone marrows that responded in vitro to the addition of interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or the combination of both. These findings suggest that the defect in AMT might be partially correctable by the administration of these cytokines. A Phase I/II trial of in vivo administration of these same hematopoietins in the identical patients was conducted in which no significant toxicity was observed. IL-3 but not GM-CSF administration resulted in improved platelet counts in two patients and decreased bleeding and transfusion requirement in the remaining three. No clinical benefit was observed when GM-CSF was administered after IL-3 pretreatment. Prolonged IL-3 administration has resulted in platelet increases in an additional two patients. In vitro responsiveness of CFU- MK to either cytokine did not predict the degree of clinical response. Although the optimal dose and schedule of IL-3 either alone or in combination remains to be established, this study suggests that IL-3 may contribute to the treatment of patients with AMT.

scholarly journals Effects of interleukin-3 and granulocyte-macrophage colony-stimulating factor on thrombopoiesis in congenital amegakaryocytic thrombocytopenia

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1691-1698 ◽  
Author(s):  
EC Guinan ◽  
YS Lee ◽  
KD Lopez ◽  
S Kohler ◽  
DH Oette ◽  
...  
Keyword(s):  
Optimal Dose ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Significant Toxicity ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Amegakaryocytic thrombocytopenia (AMT) is a rare and often fatal disorder of infancy and childhood presenting with isolated thrombocytopenia that progresses to marrow failure. The defect in thrombopoiesis is not well understood nor is the etiology of the progressive marrow failure. No standard modality of treatment exists. Here, we evaluated the capacity of marrow cells isolated from five patients with AMT and progressive marrow failure to generate megakaryocyte progenitor cells (CFU-MK). These in vitro studies demonstrated assayable numbers of CFU-MK from all patient bone marrows that responded in vitro to the addition of interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or the combination of both. These findings suggest that the defect in AMT might be partially correctable by the administration of these cytokines. A Phase I/II trial of in vivo administration of these same hematopoietins in the identical patients was conducted in which no significant toxicity was observed. IL-3 but not GM-CSF administration resulted in improved platelet counts in two patients and decreased bleeding and transfusion requirement in the remaining three. No clinical benefit was observed when GM-CSF was administered after IL-3 pretreatment. Prolonged IL-3 administration has resulted in platelet increases in an additional two patients. In vitro responsiveness of CFU- MK to either cytokine did not predict the degree of clinical response. Although the optimal dose and schedule of IL-3 either alone or in combination remains to be established, this study suggests that IL-3 may contribute to the treatment of patients with AMT.

scholarly journals Hematopoiesis in mice lacking the entire granulocyte-macrophage colony- stimulating factor/interleukin-3/interleukin-5 functions

Blood ◽  
1996 ◽  
Vol 88 (7) ◽  
pp. 2458-2464 ◽  
Author(s):  
R Nishinakamura ◽  
A Miyajima ◽  
PJ Mee ◽  
VL Tybulewicz ◽  
R Murray
Keyword(s):  
T Cells ◽  
Double Mutant ◽  
Mutant Mice ◽  
Colony Stimulating Factor ◽  
Activated T Cells ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5 are major hematopoietic cytokines produced by activated T cells and exhibit similar biologic activities by signaling through a common receptor subunit (beta c). Mice lacking beta c show a pulmonary alveolar proteinosis-like disease and reduced numbers of peripheral eosinophils, which are explained by the lack of GM-CSF and IL-5 function, respectively. However, beta c-deficient hematopoietic cells do respond to IL-3 normally, probably through an additional beta subunit of the IL-3 receptor (beta IL3) that is present in the mouse. Thus, almost normal hematopoiesis in beta c-deficient mice may be caused by functional redundancy between IL-3 and GM-CSF. To clarify the role of the entire IL-3/GM-CSF/IL-5 system in hematopoiesis in vivo, we crossed the beta c mutant mice with mice deficient for IL-3 ligand to generate mice lacking the entire IL-3/GM-CSF/IL-5 functions. The double-mutant mice were apparently normal and fertile. The severity of the lung pathology in the beta c/IL-3 double-mutant mice showed normal hemodynamic parameters except for reduced numbers of eosinophils and the lack of eosinophilic response to parasites, which were also found in beta c mutant mice. The immune response of the beta c/IL-3 double-mutant mice to Listeria mono-cytogenes was normal, as was hematopoietic recovery after administration of the cytotoxic drug, 5-fluorouracil. Although it has been believed that IL-3/GM-CSF/IL-5 produced by activated T cells play a major role in expansion of hematopoietic cells in emergency, our results indicate that the entire function of IL-3/GM- CSF/IL-5 is dispensable for hematopoiesis in emergency as well as in the steady state. Thus, there must be an alternative mechanism to produce blood cells in both situations.

scholarly journals Dexamethasone and 1,25-dihydroxyvitamin D3, but not cyclosporine A, inhibit production of granulocyte-macrophage colony-stimulating factor in human fibroblasts

Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 1912-1918
Author(s):  
A Tobler ◽  
HP Marti ◽  
C Gimmi ◽  
AB Cachelin ◽  
S Saurer ◽  
...  
Keyword(s):  
Human Fibroblasts ◽  
Tnf Alpha ◽  
Colony Stimulating Factor ◽  
Dihydroxyvitamin D3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Csf Production

Tumor necrosis factor alpha (TNF alpha) stimulates granulocyte- macrophage colony-stimulating factor (GM-CSF) production in human fibroblasts and other mesenchymal cells. However, relatively little is known about agents that downregulate cytokine production in these cells. In the present report we show that dexamethasone (Dexa), a synthetic glucocorticoid, markedly reduced GM-CSF production in TNF alpha-stimulated fibroblasts at both the protein and the RNA levels. CSF activity, GM-CSF protein, and RNA levels, determined by an in vitro colony-forming assay in normal human bone marrow cells, by an enzyme immunoassay, and by Northern blotting assay, were reduced to greater than 90% of control values by Dexa (1 mumol/L). Similarly, 1,25- dihydroxyvitamin D3 [1,25(OH)2D3], a hormone with possible physiologic immunoregulatory significance, reduced GM-CSF expression in a concentration- and time-dependent manner. However, this repression was less pronounced than that of Dexa, and in part due to a decreased proliferative activity. In contrast, cyclosporine A (CsA), another immunosuppressive agent, did not alter GM-CSF expression in TNF alpha- stimulated fibroblasts. Our in vitro studies suggest that by inhibiting GM-CSF production in fibroblasts, glucocorticoids and possibly 1,25(OH)2D3, but not CsA, may attenuate TNF alpha-mediated inflammatory processes and influence the regulation of hematopoiesis.

scholarly journals Enhanced marrow recovery by short preincubation of marrow allografts with human recombinant interleukin-3 and granulocyte-macrophage colony- stimulating factor

Blood ◽  
1992 ◽  
Vol 80 (7) ◽  
pp. 1673-1678 ◽  
Author(s):  
E Naparstek ◽  
Y Hardan ◽  
M Ben-Shahar ◽  
A Nagler ◽  
R Or ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Study Group ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Duration Of Hospitalization ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract We studied an alternative method of using hematopoietic growth factors (HGFs) to enhance hematopoietic recovery in patients undergoing bone marrow transplantation (BMT), by short in vitro preincubation. Twenty consecutive patients with leukemia received T-cell-depleted allografts using Campath-1G. Two thirds of the marrow was infused on the scheduled day of transplant and one third of the marrow following preincubation with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) on day 4. Engraftment parameters and duration of hospitalization were compared by actuarial analysis to those of 40 historical controls. Patients receiving the incubated boost had significantly faster platelet recovery (P = .017) and shorter hospitalization period (P = .001) when compared with the control subjects. Platelet count reached greater than 25 x 10(9)/L on day 17 (median) in the study group and on day 23 in the controls. The median duration of hospitalization was 20 and 36 days, respectively. In the early posttransplantation follow-up, two of four patients in the study group died as a result of graft rejection, while all 13 deaths in the control group resulted from complications associated with marrow suppression. We suggest that pretransplant in vitro activation of bone marrow cells with IL-3 and GM-CSF may prove to be an efficient method for enhancing marrow recovery after BMT.

scholarly journals Identification through chemical cross-linking of distinct granulocyte- macrophage colony-stimulating factor and interleukin-3 receptors on myeloid leukemic cells, KG-1

Blood ◽  
1989 ◽  
Vol 74 (8) ◽  
pp. 2652-2656 ◽  
Author(s):  
T Gesner ◽  
RA Mufson ◽  
KJ Turner ◽  
SC Clark
Keyword(s):  
Binding Proteins ◽  
Myelogenous Leukemia ◽  
Cross Linking ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Chemical Cross Linking

Abstract Granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) each bind specifically to a small number of high- affinity receptors present on the surface of the cells of the acute myelogenous leukemia line, KG-1. Through chemical cross-linking of IL-3 and GM-CSF to KG-1 cells, we identified distinct binding proteins for each of these cytokines with approximate molecular masses of 69 and 93 Kd, respectively. Although these two binding proteins are distinct, GM- CSF and IL-3 compete with each other for binding to KG-1 cells. Other cell lines, which express receptors for either factor but not for both do not display this cross-competition for binding with IL-3 and GM-CSF. These findings imply that distinct IL-3 and GM-CSF binding proteins are expressed on the cell surface and that an association exists between these proteins on KG-1 cells.

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