scholarly journals Gamma-interferon modulates human monocyte/macrophage transferrin receptor expression

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1590-1595 ◽  
Author(s):  
R Taetle ◽  
JM Honeysett
Keyword(s):  
Binding Sites ◽  
Blood Cells ◽  
Interleukin 1 ◽  
Human Monocyte ◽  
Gamma Interferon ◽  
Receptor Expression ◽  
Biologically Active ◽  
Gm Csf ◽  
Fe Content ◽  
Slot Blot Analysis

Abstract Although circulating human monocytes do not express transferrin (Tf) receptors, cultured adherent blood cells display high-affinity Tf binding sites. In the present studies, effects of various cytokines and biologically active proteins on human monocyte/macrophage Tf receptors were investigated. After culture, Tf receptor expression by adherent blood cells was time dependent and plateaued by 7 days. The addition of interleukin-1 (IL-1), alpha-interferon (alpha-IFN), granulocyte/macrophage-colony stimulating factor (GM-CSF), or human IgG to macrophages cultured for 4 days did not alter Tf receptor expression. Fe-saturated, human Tf caused a significant, dose-dependent decrease in receptor expression. At a dose of 100 U/mL, gamma- interferon (gamma-IFN) significantly increased Tf receptor expression by macrophages cultured for 4 (230% +/- 51% of control) or 7 days (150% +/- 22%). Scatchard analyses showed increased binding sites but no change in receptor affinity. Northern and slot blot analysis of cellular mRNA from macrophages cultured for 4 to 7 days and exposed to gamma-IFN showed a two- to fivefold increase in Tf receptor mRNA, but less than or equal to 30% increase in beta-actin mRNA. Ferritin content of gamma-IFN-treated macrophages was 47% to 63% of control cells. Net uptake of 59Fe from Tf by gamma-IFN-treated cells was 10% to 17% of control, but uptake of radiolabeled Tf was comparable. When macrophages were labeled with 59Fe and then exposed to gamma-IFN, cell-associated Fe was reduced by 43%, indicating that gamma-IFN caused macrophage Fe release. gamma-IFN specifically modulates Tf receptor display by inducing Fe release and reducing cellular Fe content. Regulation of Tf receptor expression in macrophages is controlled by cellular Fe content and is thus similar to regulatory mechanisms in dividing cells.

scholarly journals Gamma-interferon modulates human monocyte/macrophage transferrin receptor expression

Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1590-1595 ◽  
Author(s):  
R Taetle ◽  
JM Honeysett
Keyword(s):  
Binding Sites ◽  
Blood Cells ◽  
Interleukin 1 ◽  
Human Monocyte ◽  
Gamma Interferon ◽  
Receptor Expression ◽  
Biologically Active ◽  
Gm Csf ◽  
Fe Content ◽  
Slot Blot Analysis

Although circulating human monocytes do not express transferrin (Tf) receptors, cultured adherent blood cells display high-affinity Tf binding sites. In the present studies, effects of various cytokines and biologically active proteins on human monocyte/macrophage Tf receptors were investigated. After culture, Tf receptor expression by adherent blood cells was time dependent and plateaued by 7 days. The addition of interleukin-1 (IL-1), alpha-interferon (alpha-IFN), granulocyte/macrophage-colony stimulating factor (GM-CSF), or human IgG to macrophages cultured for 4 days did not alter Tf receptor expression. Fe-saturated, human Tf caused a significant, dose-dependent decrease in receptor expression. At a dose of 100 U/mL, gamma- interferon (gamma-IFN) significantly increased Tf receptor expression by macrophages cultured for 4 (230% +/- 51% of control) or 7 days (150% +/- 22%). Scatchard analyses showed increased binding sites but no change in receptor affinity. Northern and slot blot analysis of cellular mRNA from macrophages cultured for 4 to 7 days and exposed to gamma-IFN showed a two- to fivefold increase in Tf receptor mRNA, but less than or equal to 30% increase in beta-actin mRNA. Ferritin content of gamma-IFN-treated macrophages was 47% to 63% of control cells. Net uptake of 59Fe from Tf by gamma-IFN-treated cells was 10% to 17% of control, but uptake of radiolabeled Tf was comparable. When macrophages were labeled with 59Fe and then exposed to gamma-IFN, cell-associated Fe was reduced by 43%, indicating that gamma-IFN caused macrophage Fe release. gamma-IFN specifically modulates Tf receptor display by inducing Fe release and reducing cellular Fe content. Regulation of Tf receptor expression in macrophages is controlled by cellular Fe content and is thus similar to regulatory mechanisms in dividing cells.

scholarly journals Expression of colony-stimulating factor genes by normal human mesothelial cells and human malignant mesothelioma cells lines in vitro

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 940-946 ◽  
Author(s):  
GD Demetri ◽  
BW Zenzie ◽  
JG Rheinwald ◽  
JD Griffin
Keyword(s):  
Cell Lines ◽  
Malignant Mesothelioma ◽  
Interleukin 1 ◽  
Mesothelial Cells ◽  
Biologically Active ◽  
Northern Analysis ◽  
Early Passage ◽  
Gm Csf ◽  
Normal Human ◽  
Mesothelioma Cell

We investigated normal human mesothelial cells and human malignant mesothelioma cell lines for the ability to produce hematopoietic colony- stimulating factors (CSFs) in culture. Early passage cultures of normal diploid human mesothelial cells spontaneously expressed detectable levels of M-CSF mRNA transcripts, but lacked detectable transcripts for GM-CSF or G-CSF. Exposure of normal mesothelial cells to epidermal growth factor (EGF), lipopolysaccharide (LPS), or tumor necrosis factor (TNF) induced expression of G-CSF mRNA. The combination of EGF and TNF induced threefold more G-CSF transcripts than did either factor alone. GM-CSF transcripts were induced only by the combination of TNF and EGF. Interleukin-1 beta (IL-1 beta) transcripts were induced by EGF, TNF, or LPS and were inhibited by hydrocortisone (HC). All malignant mesothelioma cell lines tested also spontaneously expressed M-CSF transcripts. However, in contrast to normal mesothelial cells, two of four malignant mesothelioma cell lines also autonomously expressed G- CSF and GM-CSF transcripts without TNF, EGF, or LPS stimulation. Secretion of biologically active CSFs was confirmed by testing media conditioned by the various cell types examined. The detection of biologically active CSFs correlated well with the presence of detectable CSF transcripts by Northern analysis. These data indicate that (a) normal human mesothelial cells spontaneously express detectable levels of M-CSF mRNA in culture; (b) EGF is an essential cofactor for optimal induction of G-CSF and GM-CSF expression; (c) exposure of normal mesothelial cells to inflammatory mediators such as LPS and TNF increases the levels of transcripts for CSFs and IL-1 beta; and (d) as compared with normal human mesothelial cells, some cell lines of human malignant mesothelioma exhibit aberrant gene expression for multiple cytokines, including G-CSF, GM-CSF, IL-1 beta, and IL-6.

scholarly journals Inhibition of human erythroid colony-forming units by gamma interferon can be corrected by recombinant human erythropoietin [see comments]

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2564-2567 ◽  
Author(s):  
RT Jr Means ◽  
SB Krantz
Keyword(s):  
Chronic Disease ◽  
Interleukin 1 ◽  
Gamma Interferon ◽  
Receptor Expression ◽  
Recombinant Erythropoietin ◽  
Anemia Of Chronic Disease ◽  
Human Erythropoietin ◽  
Colony Forming Units

Abstract Tumor necrosis factor (TNF), interleukin-1 (IL-1), and gamma interferon (gamma IFN) inhibit erythropoiesis in vivo and in vitro, and have been implicated in the pathogenesis of the anemia of chronic disease. Anemia in patients with rheumatoid arthritis and in animals exposed chronically to IL-1 and TNF can be corrected by the administration of recombinant erythropoietin (Epo). We exposed highly purified human erythroid colony-forming units (CFU-E) cultured from peripheral blood burst-forming units-erythroid (BFU-E) and unpurified human marrow CFU-E to recombinant human gamma IFN and showed inhibition of colony formation in vitro. This inhibition was reversed by increased concentrations of Epo. The mechanisms by which this effect occurs are unknown at present. Epo may cause a downregulation of gamma IFN receptor expression on CFU-E or, alternatively, gamma IFN may cause a downregulation of Epo receptor expression. A full understanding of these mechanisms awaits a more complete comprehension of the regulation of erythropoiesis; however, the effect of Epo in vitro is similar to its ability to correct the anemia of chronic disease in vivo.

scholarly journals Expression of colony-stimulating factor genes by normal human mesothelial cells and human malignant mesothelioma cells lines in vitro

Blood ◽  
1989 ◽  
Vol 74 (3) ◽  
pp. 940-946 ◽  
Author(s):  
GD Demetri ◽  
BW Zenzie ◽  
JG Rheinwald ◽  
JD Griffin
Keyword(s):  
Cell Lines ◽  
Malignant Mesothelioma ◽  
Interleukin 1 ◽  
Mesothelial Cells ◽  
Biologically Active ◽  
Northern Analysis ◽  
Early Passage ◽  
Gm Csf ◽  
Normal Human ◽  
Mesothelioma Cell

Abstract We investigated normal human mesothelial cells and human malignant mesothelioma cell lines for the ability to produce hematopoietic colony- stimulating factors (CSFs) in culture. Early passage cultures of normal diploid human mesothelial cells spontaneously expressed detectable levels of M-CSF mRNA transcripts, but lacked detectable transcripts for GM-CSF or G-CSF. Exposure of normal mesothelial cells to epidermal growth factor (EGF), lipopolysaccharide (LPS), or tumor necrosis factor (TNF) induced expression of G-CSF mRNA. The combination of EGF and TNF induced threefold more G-CSF transcripts than did either factor alone. GM-CSF transcripts were induced only by the combination of TNF and EGF. Interleukin-1 beta (IL-1 beta) transcripts were induced by EGF, TNF, or LPS and were inhibited by hydrocortisone (HC). All malignant mesothelioma cell lines tested also spontaneously expressed M-CSF transcripts. However, in contrast to normal mesothelial cells, two of four malignant mesothelioma cell lines also autonomously expressed G- CSF and GM-CSF transcripts without TNF, EGF, or LPS stimulation. Secretion of biologically active CSFs was confirmed by testing media conditioned by the various cell types examined. The detection of biologically active CSFs correlated well with the presence of detectable CSF transcripts by Northern analysis. These data indicate that (a) normal human mesothelial cells spontaneously express detectable levels of M-CSF mRNA in culture; (b) EGF is an essential cofactor for optimal induction of G-CSF and GM-CSF expression; (c) exposure of normal mesothelial cells to inflammatory mediators such as LPS and TNF increases the levels of transcripts for CSFs and IL-1 beta; and (d) as compared with normal human mesothelial cells, some cell lines of human malignant mesothelioma exhibit aberrant gene expression for multiple cytokines, including G-CSF, GM-CSF, IL-1 beta, and IL-6.

scholarly journals Inhibition of human erythroid colony-forming units by gamma interferon can be corrected by recombinant human erythropoietin [see comments]

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2564-2567 ◽  
Author(s):  
RT Jr Means ◽  
SB Krantz
Keyword(s):  
Chronic Disease ◽  
Interleukin 1 ◽  
Gamma Interferon ◽  
Receptor Expression ◽  
Recombinant Erythropoietin ◽  
Anemia Of Chronic Disease ◽  
Human Erythropoietin ◽  
Colony Forming Units

Tumor necrosis factor (TNF), interleukin-1 (IL-1), and gamma interferon (gamma IFN) inhibit erythropoiesis in vivo and in vitro, and have been implicated in the pathogenesis of the anemia of chronic disease. Anemia in patients with rheumatoid arthritis and in animals exposed chronically to IL-1 and TNF can be corrected by the administration of recombinant erythropoietin (Epo). We exposed highly purified human erythroid colony-forming units (CFU-E) cultured from peripheral blood burst-forming units-erythroid (BFU-E) and unpurified human marrow CFU-E to recombinant human gamma IFN and showed inhibition of colony formation in vitro. This inhibition was reversed by increased concentrations of Epo. The mechanisms by which this effect occurs are unknown at present. Epo may cause a downregulation of gamma IFN receptor expression on CFU-E or, alternatively, gamma IFN may cause a downregulation of Epo receptor expression. A full understanding of these mechanisms awaits a more complete comprehension of the regulation of erythropoiesis; however, the effect of Epo in vitro is similar to its ability to correct the anemia of chronic disease in vivo.

High-affinity binding of PDGF-AA and PDGF-BB to normal human osteoblastic cells and modulation by interleukin-1

1991 ◽  
Vol 261 (6) ◽  
pp. C980-C985 ◽  
Author(s):  
R. S. Gilardetti ◽  
M. S. Chaibi ◽  
J. Stroumza ◽  
S. R. Williams ◽  
H. N. Antoniades ◽  
...  
Keyword(s):  
Biological Activity ◽  
Growth Factors ◽  
Binding Sites ◽  
Thymidine Incorporation ◽  
Interleukin 1 ◽  
Biologically Active ◽  
Osteoblastic Cells ◽  
High Affinity ◽  
Normal Human ◽  
Human Osteoblastic Cells

Bone has the capacity for repair and regeneration. The repair process is thought to be locally regulated by growth factors. One of the growth factors that potentially plays a significant role in these processes is platelet-derived growth factor (PDGF). Two different PDGF genes have been identified, PDGF-A and PDGF-B, whose gene products give rise to biologically active dimers. We now report that PDGF-AA and PDGF-BB exhibit saturable binding to normal human osteoblastic cells. By Scatchard analysis we estimate that there are approximately 43,000 PDGF-AA binding sites per cell, with a dissociation constant (Kd) of 2.2 x 10(-10)M, and 55,000 high-affinity PDGF-BB binding sites per cell, with a Kd of 1.2 x 10(-10)M. The functional consequence of PDGF binding was also assessed. PDGF-AA and PDGF-BB both stimulated migration of normal human osteoblastic cells and stimulated thymidine incorporation. To gain insight into potential transmodulation of the PDGF response, we investigated the capacity of interleukin-1 beta (IL-1 beta), a cytokine that induces bone resorption, to modulate PDGF binding and PDGF-induced biological activity. IL-1 beta significantly reduced PDGF-AA binding and significantly decreased both PDGF-AA-mediated cell migration and thymidine incorporation. In contrast, IL-1 beta had only a small effect of PDGF-BB binding and PDGF-BB-induced biological activity in normal human osteoblastic cells.

scholarly journals Tumor necrosis factor regulates the expression of granulocyte- macrophage colony-stimulating factor and interleukin-3 receptors on human acute myeloid leukemia cells

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 989-995 ◽  
Author(s):  
O Elbaz ◽  
LM Budel ◽  
H Hoogerbrugge ◽  
IP Touw ◽  
R Delwel ◽  
...  
Keyword(s):  
Binding Sites ◽  
Receptor Expression ◽  
Gm Csf ◽  
Kinase C ◽  
Human Acute Myeloid Leukemia ◽  
Macrophage Colony Stimulating Factor ◽  
Receptor Upregulation ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Necrosis Factor

Abstract Tumor necrosis factor (TNF) acts as a potent enhancer of granulocyte- macrophage colony-stimulating factor (GM-CSF)- and interleukin-3 (IL-3)- induced human acute myeloid leukemia (AML) growth in vitro. We have analyzed the effects of TNF alpha on the expression of GM-CSF and IL-3 receptors on AML cells. Incubation of blasts from seven patients with AML in serum-free medium with TNF (10(3) U/mL) and subsequent binding studies using 125I-GM-CSF and 125I-IL-3 show that TNF increases the specific binding of GM-CSF (30% to 280%) and IL-3 (40% to 600%) in all cases. From Scatchard plot analysis it appears that TNF upregulates (1) low-affinity GM-CSF binding sites, (2) common high-affinity IL-3/GM-CSF binding sites, and (3) unique (non-GM-CSF binding) IL-3 binding sites. The effect of TNF is dose dependent and is half maximal at a concentration of 100 U/mL, and becomes evident at 18 hours of incubation with TNF at 37 degrees C, but not at 0 degree C. The GM-CSF dose-response curve of AML-colony-forming units plateaus at a higher level in the presence of TNF, which indicates that additional numbers of cells become responsive to GM-CSF. Incubation of AML blasts with the phorbol ester 12–0-tetradecanoylphorbol-13-acetate or formyl-Met-Leu- Phe (protein kinase C activators) does not influence GM-CSF receptor expression, suggesting that receptor upregulation by TNF is not mediated through activation of protein kinase C. On the other hand, the protein synthesis inhibitor cycloheximide abrogates receptor upregulation induced by TNF. In contrast to these findings in AML, TNF does not upregulate GM-CSF receptor numbers on blood granulocytes or monocytes. We conclude that TNF exerts positive effects on growth factor receptor expression of hematopoietic cells.

scholarly journals In vivo effect of interleukin-1 alpha on hematopoiesis: role of colony- stimulating factor receptor modulation

Blood ◽  
1992 ◽  
Vol 80 (10) ◽  
pp. 2486-2494
Author(s):  
K Hestdal ◽  
SE Jacobsen ◽  
FW Ruscetti ◽  
CM Dubois ◽  
DL Longo ◽  
...  
Keyword(s):  
Bone Marrow Cells ◽  
Interleukin 1 ◽  
Receptor Expression ◽  
Proliferative Potential ◽  
Type I ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Receptor Modulation ◽  
Stimulating Factor

To determine the mechanism(s) by which interleukin-1 (IL-1) promotes granulopoiesis in vivo, we examined the effect of in vivo administration of IL-1 alpha on colony-stimulating factor (CSF) receptor expression on bone marrow cells (BMCs) and whether this directly correlated with progenitor cell responsiveness. Administration of IL-1 alpha to mice induced the upregulation of both granulocyte- macrophage-CSF (GM-CSF) and IL-3 receptors, which reached a maximum 24 hours after IL-1 alpha injection on unfractionated BMCs. This upregulation was more pronounced on the progenitor-enriched cell population (lineage-negative [Lin(-)]). The enhanced GM-CSF and IL-3 receptor expression directly correlated with enhanced IL-3- or GM-CSF- induced growth of colony-forming unit-culture (CFU-c) or CFU-mixture (CFU-Mix; colonies containing macrophages, granulocytes, and erythroid cells). In addition, the absolute number of high proliferative potential-colony-forming cells (HPP-CFC) was increased fivefold. In contrast, granulocyte-CSF (G-CSF)-specific binding on unfractionated BMCs was rapidly (4 hours) reduced after IL-1 alpha administration and returned to control levels by 24 hours. This reduction correlated with IL-1 alpha-induced margination of mature granulocytes (RBC-8C5hi cells), which express high levels of G-CSF receptors. IL-1 alpha treatment did not affect G-CSF receptor expression on Lin- cells. Pretreatment of mice with anti-type I IL-1 receptor antibody blocked the IL-1 alpha-induced upregulation of GM-CSF and IL-3 receptor expression on BMCs. Taken together, as one possible mechanism, IL-1 alpha in vivo may stimulate the expression of functional GM-CSF and IL- 3 receptors on BMCs indirectly, and, in concert with the induction of circulating CSF levels, may account for the ability of IL-1 alpha to stimulate hematopoiesis in vivo.

scholarly journals In vivo effect of interleukin-1 alpha on hematopoiesis: role of colony- stimulating factor receptor modulation

Blood ◽  
1992 ◽  
Vol 80 (10) ◽  
pp. 2486-2494 ◽  
Author(s):  
K Hestdal ◽  
SE Jacobsen ◽  
FW Ruscetti ◽  
CM Dubois ◽  
DL Longo ◽  
...  
Keyword(s):  
Bone Marrow Cells ◽  
Interleukin 1 ◽  
Receptor Expression ◽  
Proliferative Potential ◽  
Type I ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Receptor Modulation ◽  
Stimulating Factor

Abstract To determine the mechanism(s) by which interleukin-1 (IL-1) promotes granulopoiesis in vivo, we examined the effect of in vivo administration of IL-1 alpha on colony-stimulating factor (CSF) receptor expression on bone marrow cells (BMCs) and whether this directly correlated with progenitor cell responsiveness. Administration of IL-1 alpha to mice induced the upregulation of both granulocyte- macrophage-CSF (GM-CSF) and IL-3 receptors, which reached a maximum 24 hours after IL-1 alpha injection on unfractionated BMCs. This upregulation was more pronounced on the progenitor-enriched cell population (lineage-negative [Lin(-)]). The enhanced GM-CSF and IL-3 receptor expression directly correlated with enhanced IL-3- or GM-CSF- induced growth of colony-forming unit-culture (CFU-c) or CFU-mixture (CFU-Mix; colonies containing macrophages, granulocytes, and erythroid cells). In addition, the absolute number of high proliferative potential-colony-forming cells (HPP-CFC) was increased fivefold. In contrast, granulocyte-CSF (G-CSF)-specific binding on unfractionated BMCs was rapidly (4 hours) reduced after IL-1 alpha administration and returned to control levels by 24 hours. This reduction correlated with IL-1 alpha-induced margination of mature granulocytes (RBC-8C5hi cells), which express high levels of G-CSF receptors. IL-1 alpha treatment did not affect G-CSF receptor expression on Lin- cells. Pretreatment of mice with anti-type I IL-1 receptor antibody blocked the IL-1 alpha-induced upregulation of GM-CSF and IL-3 receptor expression on BMCs. Taken together, as one possible mechanism, IL-1 alpha in vivo may stimulate the expression of functional GM-CSF and IL- 3 receptors on BMCs indirectly, and, in concert with the induction of circulating CSF levels, may account for the ability of IL-1 alpha to stimulate hematopoiesis in vivo.

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