scholarly journals Functional activities of receptors for tumor necrosis factor-alpha on human vascular endothelial cells

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2578-2590
Author(s):  
EM Paleolog ◽  
SA Delasalle ◽  
WA Buurman ◽  
M Feldmann
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Tissue Factor ◽  
Adhesion Molecules ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Gm Csf ◽  
Cell Responses ◽  
Factor Alpha ◽  
Necrosis Factor

Tumor necrosis factor-alpha (TNF-alpha) plays a critical role in the control of endothelial cell function and hence in regulating traffic of circulating cells into tissues in vivo. Stimulation of endothelial cells in vitro by TNF-alpha increases the surface expression of leukocyte adhesion molecules, enhances cytokine production, and induces tissue factor procoagulant activity. In the present study, we have examined the relative roles of the two cell surface receptors for TNF- alpha (p55 and p75) on endothelial cells, using antibodies with both agonistic and antagonistic activities. We report that anti-p55 receptor agonistic antibody Htr-9 induces the expression of tissue factor antigen and the release of interleukin-8 (IL-8) and granulocyte- macrophage colony-stimulating factor (GM-CSF). In contrast, there is very little or no activation of endothelial cell responses by an anti- p75 agonist. TNF-alpha-induced expression of tissue factor and adhesion molecules, and release of IL-8 and GM-CSF, are decreased by antibodies with antagonistic activities for either receptor, although the effect of anti-p55 antibodies is markedly greater than that of anti-p75 antibodies. The responses of endothelial cells to lymphotoxin/TNF-beta are significantly decreased by anti-p55 antagonists alone. Our data suggest that endothelial cell responses to TNF-alpha, such as expression of tissue factor and adhesion molecules for mononuclear cells, which may be important in the pathogenesis of atherosclerosis, are mediated predominantly, but not exclusively, by the p55 TNF receptor.

scholarly journals Functional activities of receptors for tumor necrosis factor-alpha on human vascular endothelial cells

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2578-2590 ◽  
Author(s):  
EM Paleolog ◽  
SA Delasalle ◽  
WA Buurman ◽  
M Feldmann
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Tissue Factor ◽  
Adhesion Molecules ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Gm Csf ◽  
Cell Responses ◽  
Factor Alpha ◽  
Necrosis Factor

Abstract Tumor necrosis factor-alpha (TNF-alpha) plays a critical role in the control of endothelial cell function and hence in regulating traffic of circulating cells into tissues in vivo. Stimulation of endothelial cells in vitro by TNF-alpha increases the surface expression of leukocyte adhesion molecules, enhances cytokine production, and induces tissue factor procoagulant activity. In the present study, we have examined the relative roles of the two cell surface receptors for TNF- alpha (p55 and p75) on endothelial cells, using antibodies with both agonistic and antagonistic activities. We report that anti-p55 receptor agonistic antibody Htr-9 induces the expression of tissue factor antigen and the release of interleukin-8 (IL-8) and granulocyte- macrophage colony-stimulating factor (GM-CSF). In contrast, there is very little or no activation of endothelial cell responses by an anti- p75 agonist. TNF-alpha-induced expression of tissue factor and adhesion molecules, and release of IL-8 and GM-CSF, are decreased by antibodies with antagonistic activities for either receptor, although the effect of anti-p55 antibodies is markedly greater than that of anti-p75 antibodies. The responses of endothelial cells to lymphotoxin/TNF-beta are significantly decreased by anti-p55 antagonists alone. Our data suggest that endothelial cell responses to TNF-alpha, such as expression of tissue factor and adhesion molecules for mononuclear cells, which may be important in the pathogenesis of atherosclerosis, are mediated predominantly, but not exclusively, by the p55 TNF receptor.

scholarly journals Inducible production of interleukin-6 by human polymorphonuclear neutrophils: role of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 2049-2052 ◽  
Author(s):  
NA Cicco ◽  
A Lindemann ◽  
J Content ◽  
P Vandenbussche ◽  
M Lubbert ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Polymorphonuclear Neutrophils ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Gm Csf ◽  
Factor Alpha ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Necrosis Factor

Abstract The recent demonstration of the ability of human polymorphonuclear neutrophils (PMN) to secrete various cytokines in response to the granulocyte activator granulocyte-macrophage colony-stimulating factor (GM-CSF) but not to other cytokines, has led to the identification of PMN as biosynthetically active cells. In this study we have investigated the ability of PMN to secrete interleukin-6 (IL-6), a molecule known to be involved in inflammatory reactions. Using RNA blotting analysis and bioassays, we show that PMN could be induced to synthesize transcripts specific for IL-6, indistinguishable in size from IL-6 mRNA produced by activated human macrophages. Consequently, PMN released IL-6-like activity into their culture supernatants that could be neutralized by monospecific anti-IL-6 antibody. Interleukin-6 secretion by PMN, however, required previous stimulation with GM-CSF or tumor necrosis factor-alpha (TNF-alpha), whereas other cytokines, including interleukin-3 (IL-3), granulocyte-CSF (G-CSF), macrophage-CSF (M-CSF), interferon gamma (IFN-gamma), and lymphotoxin (LT), failed to induce IL-6 mRNA accumulation and protein secretion by PMN. Similar to GM-CSF and TNF-alpha, other compounds, including the inhibitor of protein synthesis cyclohexemide (CHX), endotoxin (Escherichia coli- derived lipopolysaccharide), and phorbol myristate acetate (PMA) (but not the chemoattractant N-formyl-methionyl-leucyl-phenylalanine [FMLP]), induced detectable levels of IL-6 transcripts in PMN.

scholarly journals Bifunctional effects of tumor necrosis factor alpha (TNF alpha) on the growth of mature and primitive human hematopoietic progenitor cells: involvement of p55 and p75 TNF receptors

Blood ◽  
1994 ◽  
Vol 83 (11) ◽  
pp. 3152-3159 ◽  
Author(s):  
LS Rusten ◽  
FW Jacobsen ◽  
W Lesslauer ◽  
H Loetscher ◽  
EB Smeland ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Colony Growth ◽  
Tnf Alpha ◽  
Tnf Receptors ◽  
Hematopoietic Progenitor ◽  
Necrosis Factor Alpha ◽  
Gm Csf ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Stimulation Of

Abstract Tumor necrosis factor alpha (TNF alpha) has previously been reported to have both inhibitory and stimulatory effects on hematopoietic progenitor cells. Specifically, TNF alpha has been proposed to stimulate early hematopoiesis in humans. In the present study we show that TNF alpha, in a dose-dependent fashion, can potently inhibit the growth of primitive high proliferative potential colony-forming cells (HPP-CFCs) stimulated by multiple cytokine combinations. Using agonistic antibodies to the p55 and p75 TNF receptors or TNF alpha mutants specific for either of the two TNF receptors, we show that both receptors can mediate this inhibition. In contrast, the potent stimulation of interleukin-3 (IL-3) plus granulocyte-macrophage colony- stimulating factor (GM-CSF) induced HPP-CFC colony formation observed at low concentrations of TNF alpha (2 ng/mL) was only a p55-mediated event. Moreover, the stimulatory effects of TNF alpha on GM-CSF or IL-3- induced colony formation, as well as the inhibition of G-CSF-induced colony growth, were also exclusively signaled through the p55 TNF receptor. Taken together, our results suggest that the inhibitory effects of TNF alpha on primitive bone marrow progenitor cells are mediated through both p55 and p75 TNF receptors, whereas the p55 receptor exclusively mediates the bidirectional effects on more mature, single factor-responsive bone marrow progenitor cells as well as stimulation of IL-3 plus GM-CSF-induced HPP-CFC colony growth.

scholarly journals Bacterial Lipopolysaccharide and Tumor Necrosis Factor Alpha Synergistically Increase Expression of Human Endothelial Adhesion Molecules through Activation of NF-κB and p38 Mitogen-Activated Protein Kinase Signaling Pathways

2001 ◽  
Vol 69 (3) ◽  
pp. 1273-1279 ◽  
Author(s):  
Hubertus P. A. Jersmann ◽  
Charles S. T. Hii ◽  
Judith V. Ferrante ◽  
Antonio Ferrante
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase ◽  
Adhesion Molecules ◽  
Cardiovascular Events ◽  
Tumor Necrosis ◽  
Mitogen Activated Protein Kinase ◽  
Necrosis Factor Alpha ◽  
Mitogen Activated Protein ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT One of the recognized associations of bacterial infection with cardiovascular events is the activation of endothelium and upregulation of adhesion molecules. The two major proinflammatory mediators implicated in the causation of cardiovascular events, bacterial lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF), were found to cooperate to enhance the adhesive properties of endothelial cells. These caused synergistic upregulation of intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 in human umbilical vein endothelial cells as determined by flow cytometry analysis and enzyme-linked immunosorbent assay. This synergism was not due to TNF causing an upregulation of CD14 expression. Treatment with both LPS and TNF resulted in a marked increase in the translocation of NF-κB into the nucleus. The activity of p38 mitogen-activated protein kinase was also synergistically enhanced, while the activity of c-jun N-terminal kinase was increased in an additive manner. The results demonstrate that LPS and TNF act synergistically to upregulate the expression of endothelial cell adhesion molecules, possibly by amplification of signaling pathways upstream of transcription. These findings have implications for the understanding of the acceleration of atherosclerotic events seen in low-grade infections with gram-negative organisms.

scholarly journals Bifunctional effects of tumor necrosis factor alpha (TNF alpha) on the growth of mature and primitive human hematopoietic progenitor cells: involvement of p55 and p75 TNF receptors

Blood ◽  
1994 ◽  
Vol 83 (11) ◽  
pp. 3152-3159 ◽  
Author(s):  
LS Rusten ◽  
FW Jacobsen ◽  
W Lesslauer ◽  
H Loetscher ◽  
EB Smeland ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Colony Growth ◽  
Tnf Alpha ◽  
Tnf Receptors ◽  
Hematopoietic Progenitor ◽  
Necrosis Factor Alpha ◽  
Gm Csf ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Stimulation Of

Tumor necrosis factor alpha (TNF alpha) has previously been reported to have both inhibitory and stimulatory effects on hematopoietic progenitor cells. Specifically, TNF alpha has been proposed to stimulate early hematopoiesis in humans. In the present study we show that TNF alpha, in a dose-dependent fashion, can potently inhibit the growth of primitive high proliferative potential colony-forming cells (HPP-CFCs) stimulated by multiple cytokine combinations. Using agonistic antibodies to the p55 and p75 TNF receptors or TNF alpha mutants specific for either of the two TNF receptors, we show that both receptors can mediate this inhibition. In contrast, the potent stimulation of interleukin-3 (IL-3) plus granulocyte-macrophage colony- stimulating factor (GM-CSF) induced HPP-CFC colony formation observed at low concentrations of TNF alpha (2 ng/mL) was only a p55-mediated event. Moreover, the stimulatory effects of TNF alpha on GM-CSF or IL-3- induced colony formation, as well as the inhibition of G-CSF-induced colony growth, were also exclusively signaled through the p55 TNF receptor. Taken together, our results suggest that the inhibitory effects of TNF alpha on primitive bone marrow progenitor cells are mediated through both p55 and p75 TNF receptors, whereas the p55 receptor exclusively mediates the bidirectional effects on more mature, single factor-responsive bone marrow progenitor cells as well as stimulation of IL-3 plus GM-CSF-induced HPP-CFC colony growth.

scholarly journals Tumor necrosis factor-alpha modulation of glycoprotein Ib alpha expression in human endothelial and erythroleukemia cells

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 153-161 ◽  
Author(s):  
V Rajagopalan ◽  
DW Essex ◽  
SS Shapiro ◽  
BA Konkle
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Protein Expression ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Mrna Level ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Abstract Glycoprotein Ib alpha (GpIb alpha) is a platelet membrane Gp that binds von Willebrand factor and mediates platelet adhesion to subendothelium. We have found both GpIb alpha mRNA and protein in human umbilical vein endothelial cells (HUVEC). In previously published work we reported that combined treatment with interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) markedly increased the GpIb alpha mRNA level in HUVEC. We have now documented that TNF-alpha alone induces GpIb alpha mRNA and protein expression, studied the kinetics of this response, and investigated potential mechanisms of the TNF-alpha effect. GpIb alpha mRNA induction by TNF-alpha is detectable as early as 2 hours after exposure to this cytokine, and reaches a maximal level after 20 to 24 hours. Using a nuclear run-on assay we found that GpIb alpha gene transcription is increased approximately 10-fold after 2 hours of TNF-alpha treatment. Furthermore, using two monoclonal antibodies that recognize different epitopes of GpIb alpha, we found that the protein expression in endothelial cells is markedly increased by TNF-alpha. Interleukin-1 (IL-1) and the phorbol ester phorbol myristate acetate, which mimic many effects of TNF-alpha on endothelial cells, have no effect on endothelial or human erytholeukemia (HEL)-cell GpIb alpha mRNA. TNF-alpha treatment for 24 hours increases the HEL cell GpIb alpha mRNA level approximately fourfold, showing a time- and dose-dependent effect similar to that seen in HUVEC. TNF-alpha-induced GpIb alpha mRNA and protein synthesis may play a role in mediating platelet or other cell interaction with activated endothelium. Unlike other endothelial pro-thrombotic and pro-adhesive proteins induced by TNF-alpha, GpIb alpha is not induced by IL-1 treatment, which suggests a novel pathway for induction of this protein.

scholarly journals The receptor for interleukin 3 is selectively induced in human endothelial cells by tumor necrosis factor alpha and potentiates interleukin 8 secretion and neutrophil transmigration

1993 ◽  
Vol 90 (23) ◽  
pp. 11137-11141 ◽  
Author(s):  
E I Korpelainen ◽  
J R Gamble ◽  
W B Smith ◽  
G J Goodall ◽  
S Qiyu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Scatchard Analysis ◽  
Necrosis Factor Alpha ◽  
High Affinity ◽  
Factor Alpha ◽  
Necrosis Factor

Interleukin (IL)-3 stimulates hemopoiesis in vitro. However, IL-3 is not normally found in bone marrow, raising doubts as to the in vivo role of IL-3. We have found that human umbilical vein endothelial cells (HUVEC) express functional high-affinity receptors for IL-3 after stimulation with tumor necrosis factor alpha (TNF-alpha), IL-1 beta, or lipopolysaccharide, and that this receptor is involved in inflammatory phenomena. TNF-alpha caused time- and dose-dependent up-regulation of mRNA for the IL-3 receptor alpha and beta chains, with maximal effects occurring 16-36 h after stimulation with TNF-alpha at 100 units/ml. Induction of mRNA correlated with protein expression on the cell surface as judged by monoclonal antibody staining and by the ability of HUVEC to specifically bind 125I-labeled IL-3. Scatchard analysis under optimal conditions of TNF-alpha stimulation revealed approximately 1500 IL-3 receptors per cell, which were of a high-affinity class (Kd = 500 pM) only. In contrast to a previous report, receptors for granulocyte-macrophage colony-stimulating factor could not be detected. IL-3 binding to TNF-alpha-activated HUVEC enhanced IL-8 production, E-selection expression, and neutrophil transmigration. The selective induction of a functional IL-3 receptor on endothelial cells suggests that, beyond hemopoiesis, IL-3 may have an important role in chronic inflammation and in allergic diseases.

Tumor necrosis factor-alpha augments pulmonary arterial transendothelial albumin flux in vitro

1990 ◽  
Vol 258 (2) ◽  
pp. L57-L67 ◽  
Author(s):  
S. E. Goldblum ◽  
W. L. Sun
Keyword(s):  
Endothelial Cell ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tnf Alpha ◽  
Vascular Endothelial ◽  
Temperature Dependent ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Pulmonary Arterial ◽  
Necrosis Factor

Tumor necrosis factor-alpha (TNF alpha) has been implicated as a mediator of pulmonary vascular endothelial injury. We studied the effect of human recombinant TNF alpha (rTNF alpha) on transfer of 14C-labeled bovine serum albumin (BSA) across cultured bovine pulmonary arterial endothelial cell monolayers. rTNF alpha induced a dose-, time-, and temperature-dependent increment in transendothelial [14C]BSA flux. Only after an incubation time of greater than or equal to 4 h did rTNF alpha significantly (P less than 0.005) increase transendothelial albumin flux. rTNF alpha exposure times as brief as 5 min induced significantly (P less than 0.005) increased albumin transfer at 6 h. Although this initial rTNF alpha-endothelial interaction was not temperature dependent, the subsequent barrier dysfunction could only be generated at 37 degrees C. The rTNF alpha-induced changes could not be ascribed to endothelial cell cytotoxicity and was not blocked by protein synthesis inhibition. The effects of rTNF alpha on endothelial permeability were reversible and not specific for albumin transfer. Therefore, rTNF alpha may influence the movement of macromolecules across the pulmonary vascular endothelial barrier.

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