scholarly journals Paracrine downregulation of Fc gamma RIII in human monocyte-derived macrophages induced by phagocytosis of nonopsonized particles

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2294-2304 ◽  
Author(s):  
G Liao ◽  
J Simone ◽  
SR Simon
Keyword(s):  
Direct Contact ◽  
Human Monocyte ◽  
Tnf Alpha ◽  
Triggered Release ◽  
Necrosis Factor Alpha ◽  
Dual Channel ◽  
Latex Beads ◽  
Monocytes And Macrophages ◽  
Channel Analysis ◽  
Green Fluorescent

Abstract Monocytes and macrophages can take up nonopsonized particles through a direct phagocytic process and IgG-coated particles through combined mechanisms of nonspecific phagocytosis and internalization mediated by specific Fc receptors for IgG (Fc gamma R) on the plasma membrane. In this study, we report the effect of phagocytosis of nonopsonized latex beads on the levels of expression of Fc gamma receptors in human monocyte-derived macrophages (MDM) as measured by flow cytometry (fluorescence-activated cell sorter [FACS]). Macrophages were exposed to green fluorescent 1-micron polystyrene beads before labeling for Fc gamma RI, Fc gamma R-II, and Fc gamma R-III, respectively, with 32.2, 2E1, and 3G8 monoclonal antibodies (MoAbs) and a phycoerythrin (PE)- conjugated secondary Ab to permit dual-channel analysis of fluorescence intensity by FACS. Macrophages that had phagocytosed at least one bead showed reduced levels of surface Fc gamma R-III but not Fc gamma R-I or Fc gamma R-II when compared with cells that had never been exposed to beads. Moreover, cells that were not in direct contact with beads, but that shared medium with cells that had phagocytosed beads also had reduced levels of Fc gamma R-III but not Fc gamma R-I or Fc gamma R-II, suggesting a cytokine-mediated mechanism of Fc gamma R-III downregulation. Phagocytosis of 1-micron beads alone stimulated macrophages to release tumor necrosis factor-alpha (TNF-alpha). The medium from macrophages phagocytosing beads could stimulate other macrophages not in direct contact with beads to release TNF-alpha as well, but such paracrine-triggered release could be reduced by more than 50% if the medium from the phagocytosing cells was first treated with a neutralizing anti-TNF-alpha antibody. Moreover, the paracrine downregulation of Fc gamma R-III described above could also be blocked if the neutralizing anti-TNF-alpha antibody was added to the medium of phagocytosing cells. Treatment of macrophages with recombinant human TNF-alpha in the absence of beads induced decreased levels of Fc gamma R-III but not of Fc gamma R-II. These results show that paracrine downregulation of Fc gamma R-III is mediated by a TNF-alpha-dependent mechanism.

scholarly journals Paracrine downregulation of Fc gamma RIII in human monocyte-derived macrophages induced by phagocytosis of nonopsonized particles

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2294-2304
Author(s):  
G Liao ◽  
J Simone ◽  
SR Simon
Keyword(s):  
Direct Contact ◽  
Human Monocyte ◽  
Tnf Alpha ◽  
Triggered Release ◽  
Necrosis Factor Alpha ◽  
Dual Channel ◽  
Latex Beads ◽  
Monocytes And Macrophages ◽  
Channel Analysis ◽  
Green Fluorescent

Monocytes and macrophages can take up nonopsonized particles through a direct phagocytic process and IgG-coated particles through combined mechanisms of nonspecific phagocytosis and internalization mediated by specific Fc receptors for IgG (Fc gamma R) on the plasma membrane. In this study, we report the effect of phagocytosis of nonopsonized latex beads on the levels of expression of Fc gamma receptors in human monocyte-derived macrophages (MDM) as measured by flow cytometry (fluorescence-activated cell sorter [FACS]). Macrophages were exposed to green fluorescent 1-micron polystyrene beads before labeling for Fc gamma RI, Fc gamma R-II, and Fc gamma R-III, respectively, with 32.2, 2E1, and 3G8 monoclonal antibodies (MoAbs) and a phycoerythrin (PE)- conjugated secondary Ab to permit dual-channel analysis of fluorescence intensity by FACS. Macrophages that had phagocytosed at least one bead showed reduced levels of surface Fc gamma R-III but not Fc gamma R-I or Fc gamma R-II when compared with cells that had never been exposed to beads. Moreover, cells that were not in direct contact with beads, but that shared medium with cells that had phagocytosed beads also had reduced levels of Fc gamma R-III but not Fc gamma R-I or Fc gamma R-II, suggesting a cytokine-mediated mechanism of Fc gamma R-III downregulation. Phagocytosis of 1-micron beads alone stimulated macrophages to release tumor necrosis factor-alpha (TNF-alpha). The medium from macrophages phagocytosing beads could stimulate other macrophages not in direct contact with beads to release TNF-alpha as well, but such paracrine-triggered release could be reduced by more than 50% if the medium from the phagocytosing cells was first treated with a neutralizing anti-TNF-alpha antibody. Moreover, the paracrine downregulation of Fc gamma R-III described above could also be blocked if the neutralizing anti-TNF-alpha antibody was added to the medium of phagocytosing cells. Treatment of macrophages with recombinant human TNF-alpha in the absence of beads induced decreased levels of Fc gamma R-III but not of Fc gamma R-II. These results show that paracrine downregulation of Fc gamma R-III is mediated by a TNF-alpha-dependent mechanism.

scholarly journals Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes.

1991 ◽  
Vol 173 (3) ◽  
pp. 699-703 ◽  
Author(s):  
E P Sampaio ◽  
E N Sarno ◽  
R Galilly ◽  
Z A Cohn ◽  
G Kaplan
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Human Monocyte ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

Thalidomide selectively inhibits the production of human monocyte tumor necrosis factor alpha (TNF-alpha) when these cells are triggered with lipopolysaccharide and other agonists in culture. 40% inhibition occurs at the clinically achievable dose of the drug of 1 micrograms/ml. In contrast, the amount of total protein and individual proteins labeled with [35S]methionine and expressed on SDS-PAGE are not influenced. The amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony-stimulating factor produced by monocytes remain unaltered. The selectivity of this drug may be useful in determining the role of TNF-alpha in vivo and modulating its toxic effects in a clinical setting.

scholarly journals Modulating activity of interferon-gamma on endotoxin-induced cytokine production in cancer patients

Blood ◽  
1991 ◽  
Vol 78 (12) ◽  
pp. 3254-3258
Author(s):  
A Mackensen ◽  
C Galanos ◽  
R Engelhardt
Keyword(s):  
Cancer Patients ◽  
Interferon Gamma ◽  
Cytokine Production ◽  
Repeated Administration ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma ◽  
Lps Challenge ◽  
Monocytes And Macrophages

Intravenous (IV) administration of purified lipopolysaccharide (LPS) from Salmonella abortus equi to cancer patients induces the formation of high amounts of endogenous cytokines such as tumor necrosis factor- alpha (TNF-alpha) and interleukin-6 (IL-6). On repeated administration of LPS at 2-week intervals, a marked downregulation of the cytokine response was observed, especially between the first and the second challenge. This study sought to determine whether it would be possible to prevent this downregulation by pretreating patients with interferon- gamma (IFN-gamma), which is known to enhance cytokine production by monocytes and macrophages in vitro. Ten patients with disseminated cancer received a first injection of 4.0 ng LPS/kg. Thereafter, patients were divided into two groups. One group received two further LPS injections (4.0 ng/kg) at 2-week intervals. The second group was pretreated (-12 hours) with 50 micrograms IFN-gamma subcutaneously (SC) before the second and third LPS challenge. To prevent constitutional side effects such as fever and chills, patients received 1,600 mg ibuprofen orally before LPS injection. The results of the current study demonstrate that apart from TNF-alpha and IL-6, two other cytokines, interleukin-8 (IL-8) and granulocyte colony-stimulating factor (G-CSF) are produced in cancer patients in response to LPS. LPS application at 2-week intervals resulted in a transient attenuation of all cytokines (TNF-alpha, IL-6, IL-8, G-CSF) on the second challenge. In the case of TNF-alpha, IL-6, and G-CSF, pretreatment with IFN-gamma not only prevented the downregulation, but enhanced the production of these cytokines to levels higher than those obtained after the first LPS challenge. In contrast, the downregulation of IL-8 remained unaffected by IFN-gamma pretreatment. Further studies are warranted to determine whether the prevention of cytokine downregulation by IFN-gamma following repeated LPS injections is of clinical relevance in respect to the antitumor activity of LPS.

scholarly journals Macrophage priming and lipopolysaccharide-triggered release of tumor necrosis factor alpha during graft-versus-host disease.

1992 ◽  
Vol 175 (2) ◽  
pp. 405-413 ◽  
Author(s):  
F P Nestel ◽  
K S Price ◽  
T A Seemayer ◽  
W S Lapp
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Acute Gvhd ◽  
Tnf Alpha ◽  
Triggered Release ◽  
Necrosis Factor Alpha ◽  
Alpha Production ◽  
Factor Alpha ◽  
Necrosis Factor

In this report we have investigated macrophage (M phi) activity and tumor necrosis factor alpha (TNF-alpha) production during graft-vs.-host disease (GVHD). TNF-alpha production by M phi requires two signals: priming of M phi by interferon followed by triggering of TNF-alpha production and release by lipopolysaccharide (LPS). The state of M phi activation was examined in nonirradiated B6AF1 recipient mice injected with either 60 x 10(6) (acute GVHD) or 30 x 10(6) (nonlethal GVHD) parental B6 lymphoid cells. During the early phase of acute GVHD, administration of normally sublethal amounts of LPS-triggered release of significant amounts of TNF-alpha into the serum resulting in death of the animals within 36 h. Normal animals treated with the same dose of LPS neither died nor produced detectable amounts of serum TNF-alpha. In vitro studies demonstrated that M phi were primed during GVHD. The level of M phi priming was greater during acute GVHD than nonlethal GVHD since 100-fold less LPS was required to trigger killing of a TNF-alpha-sensitive cell line by M phi from acute GVHD animals. The amount of TNF-alpha released into the serum after LPS injection increased during the course of the GVHD and was significantly greater in acute GVH-reactive mice. Endogenous LPS was detected in the serum of acute GVH-reactive animals coincident with the onset of mortality. The data provide evidence that during GVHD M phi are primed as a result of the allogeneic reaction and that endogenous LPS therefore triggers M phi production of TNF-alpha resulting in the symptoms characteristic of acute GVHD.

scholarly journals Modulating activity of interferon-gamma on endotoxin-induced cytokine production in cancer patients

Blood ◽  
1991 ◽  
Vol 78 (12) ◽  
pp. 3254-3258 ◽  
Author(s):  
A Mackensen ◽  
C Galanos ◽  
R Engelhardt
Keyword(s):  
Cancer Patients ◽  
Interferon Gamma ◽  
Cytokine Production ◽  
Repeated Administration ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma ◽  
Lps Challenge ◽  
Monocytes And Macrophages

Abstract Intravenous (IV) administration of purified lipopolysaccharide (LPS) from Salmonella abortus equi to cancer patients induces the formation of high amounts of endogenous cytokines such as tumor necrosis factor- alpha (TNF-alpha) and interleukin-6 (IL-6). On repeated administration of LPS at 2-week intervals, a marked downregulation of the cytokine response was observed, especially between the first and the second challenge. This study sought to determine whether it would be possible to prevent this downregulation by pretreating patients with interferon- gamma (IFN-gamma), which is known to enhance cytokine production by monocytes and macrophages in vitro. Ten patients with disseminated cancer received a first injection of 4.0 ng LPS/kg. Thereafter, patients were divided into two groups. One group received two further LPS injections (4.0 ng/kg) at 2-week intervals. The second group was pretreated (-12 hours) with 50 micrograms IFN-gamma subcutaneously (SC) before the second and third LPS challenge. To prevent constitutional side effects such as fever and chills, patients received 1,600 mg ibuprofen orally before LPS injection. The results of the current study demonstrate that apart from TNF-alpha and IL-6, two other cytokines, interleukin-8 (IL-8) and granulocyte colony-stimulating factor (G-CSF) are produced in cancer patients in response to LPS. LPS application at 2-week intervals resulted in a transient attenuation of all cytokines (TNF-alpha, IL-6, IL-8, G-CSF) on the second challenge. In the case of TNF-alpha, IL-6, and G-CSF, pretreatment with IFN-gamma not only prevented the downregulation, but enhanced the production of these cytokines to levels higher than those obtained after the first LPS challenge. In contrast, the downregulation of IL-8 remained unaffected by IFN-gamma pretreatment. Further studies are warranted to determine whether the prevention of cytokine downregulation by IFN-gamma following repeated LPS injections is of clinical relevance in respect to the antitumor activity of LPS.

The Evaluation of the Role of the Cytokines TNF- alfa and IL 6 in the Production of Hypoalbuminemia in Patients Undergoing Major Surgical Interventions

2018 ◽  
Vol 69 (7) ◽  
pp. 1830-1837
Author(s):  
Cristian Nicolescu ◽  
Alaxendru Pop ◽  
Alin Mihu ◽  
Luminita Pilat ◽  
Ovidiu Bedreag ◽  
...  
Keyword(s):  
Surgical Procedure ◽  
Tnf Alpha ◽  
Phase Reaction ◽  
Statistical Validation ◽  
Necrosis Factor Alpha ◽  
Surgical Interventions ◽  
Plasmatic Level ◽  
Factor Alpha ◽  
Validation Tests

This article presents an observational randomized prospective study done on 65 patients, who underwent major surgical interventions in the field of orthopedic surgery-total hip replacement or general surgery � total colectomy. The level of albuminemia in these cases were determined before the surgical intervention, after 6 hours of the intervention and after 24 h of the intervention. The measurements of the plasmatic concentration of the pro-inflammatory cytokines Tumor Necrosis factor -alpha (TNF-alpha) and interleukin 6 (IL6) were simultaneously done with the determination of the plasmatic levels of albumin. Values of hemoglobin and hematocrit were determined 24 h after the surgical procedure in order to exclude hemodilution, which could lead to a possible drop in the levels of plasmatic albumin. After the collection of the data, the statistical work was done and it consisted of descriptive statistics, correlation and comparison tests as well as statistical validation tests. Obtained results indicate that IL-6 plays a major role comparatively with that of TNF-alfa, regarding the decrease of the plasmatic level of albumin, and due to this, the primordial cause for hypoalbuminemia is an acute hepatic phase reaction. Supplemental permeability of the capillary wall under the action of TNF alpha has a secondary role, but could lead to a faster decrease in plasmatic albumin in the first hours after the surgical procedure.

Tumor necrosis factor-alpha inhibits lipid and lipoprotein transport by Caco-2 cells

1995 ◽  
Vol 269 (6) ◽  
pp. G953-G960 ◽  
Author(s):  
M. Mehran ◽  
E. Seidman ◽  
R. Marchand ◽  
C. Gurbindo ◽  
E. Levy
Keyword(s):  
Lipid Metabolism ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Low Density Lipoproteins ◽  
Tnf Alpha ◽  
Low Density ◽  
Necrosis Factor Alpha ◽  
Apo B ◽  
Factor Alpha ◽  
Necrosis Factor

Cytokines, important mediators of inflammation, have been shown to cause disturbances in circulating and hepatic lipid metabolism. Although the intestine plays a major role in dietary fat transport and largely contributes to plasma lipoproteins, the effects of cytokines on intestinal lipid handling remain unknown. In the present study, the modulation of lipid, apoprotein, and lipoprotein synthesis and secretion by tumor necrosis factor-alpha (TNF-alpha) was investigated in Caco-2 cells. Highly differentiated and polarized cells (20 days in culture) were incubated for 20 h with recombinant human TNF-alpha (100-500 ng/ml). No cytotoxic effect of TNF-alpha cells was observed, as indicated by the determinations of Caco-2 cell viability and monolayer transepithelial resistance. Moreover, no differences in cell maturation (sucrase activity) or cell proliferation ([3H]thymidine incorporation and cell cycle analysis) were detected between treated and control cultures. Significant inhibition of lipid secretion by TNF-alpha was observed, with the greatest reduction at 500 ng/ml. TNF-alpha significantly decreased Caco-2 cell secretion of phospholipids (22%), triglycerides (30%), and cholesteryl ester (37%). It also significantly diminished the export of newly synthesized low-density lipoproteins (LDL; 20%) and high-density lipoproteins (HDL; 13%), with a lesser effect on very low-density lipoproteins (VLDL; 3%). The lipid composition of these lipoproteins was minimally affected. De novo synthesis of apo A-I, apo B-100, and apo B-48 was also markedly reduced by TNF-alpha. Sphingomyelinase activity was not increased and cell content of sphingomyelin was not altered, suggesting that inhibitory effects on lipid and apoprotein of TNF-alpha were not mediated by the ceramide pathway. Our results indicate that TNF-alpha may play a role in modulating intestinal lipid metabolism, thus affecting circulating lipoproteins.

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