Maturation of dendritic cells leads to up-regulation of cellular FLICE-inhibitory protein and concomitant down-regulation of death ligand–mediated apoptosis

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2628-2631 ◽  
Author(s):  
Martin Leverkus ◽  
Henning Walczak ◽  
Alex McLellan ◽  
Hans-Werner Fries ◽  
Gabi Terbeck ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis ◽  
Caspase 8 ◽  
Inhibitory Protein ◽  
Cd95 Ligand ◽  
Induction Of Apoptosis ◽  
Low Levels ◽  
Necrosis Factor ◽  
Dc Maturation

Abstract Dendritic cells (DCs) disappear from lymph nodes 1 to 2 days after antigen presentation, presumably by apoptosis. To evaluate the role of death ligands in elimination of DCs, we analyzed the sensitivity of human DCs to CD95 ligand (CD95L) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We found mature DCs to be resistant to killing via CD95L or TRAIL, whereas only immature DCs were partially sensitive. However, all DC populations expressed CD95, TRAIL-R2, and TRAIL-R3 at comparable levels, suggesting that sensitivity to death ligand-induced DC apoptosis is not regulated at the receptor level. Interestingly, mature DCs highly expressed the caspase 8 inhibitory protein cFLIP, whereas only low levels were detected in immature DCs. Thus, death ligand sensitivity proved to be dependent on DC maturation and inversely correlated with expression levels of cFLIP. Induction of apoptosis by TRAIL or CD95L does not seem to play a role in the elimination of mature DCs, but instead might serve to regulate immature DC populations.

Maturation of dendritic cells leads to up-regulation of cellular FLICE-inhibitory protein and concomitant down-regulation of death ligand–mediated apoptosis

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2628-2631 ◽  
Author(s):  
Martin Leverkus ◽  
Henning Walczak ◽  
Alex McLellan ◽  
Hans-Werner Fries ◽  
Gabi Terbeck ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis ◽  
Caspase 8 ◽  
Inhibitory Protein ◽  
Cd95 Ligand ◽  
Induction Of Apoptosis ◽  
Low Levels ◽  
Necrosis Factor ◽  
Dc Maturation

Dendritic cells (DCs) disappear from lymph nodes 1 to 2 days after antigen presentation, presumably by apoptosis. To evaluate the role of death ligands in elimination of DCs, we analyzed the sensitivity of human DCs to CD95 ligand (CD95L) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We found mature DCs to be resistant to killing via CD95L or TRAIL, whereas only immature DCs were partially sensitive. However, all DC populations expressed CD95, TRAIL-R2, and TRAIL-R3 at comparable levels, suggesting that sensitivity to death ligand-induced DC apoptosis is not regulated at the receptor level. Interestingly, mature DCs highly expressed the caspase 8 inhibitory protein cFLIP, whereas only low levels were detected in immature DCs. Thus, death ligand sensitivity proved to be dependent on DC maturation and inversely correlated with expression levels of cFLIP. Induction of apoptosis by TRAIL or CD95L does not seem to play a role in the elimination of mature DCs, but instead might serve to regulate immature DC populations.

scholarly journals Distinct Roles of Lymphotoxin α and the Type I Tumor Necrosis Factor (TNF) Receptor in the Establishment of Follicular Dendritic Cells from Non–Bone Marrow–derived Cells

1997 ◽  
Vol 186 (12) ◽  
pp. 1997-2004 ◽  
Author(s):  
Mitsuru Matsumoto ◽  
Yang-Xin Fu ◽  
Hector Molina ◽  
Guangming Huang ◽  
Jinho Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Tumor Necrosis ◽  
Type I ◽  
Follicular Dendritic Cells ◽  
Wild Type ◽  
Lymphotoxin Α ◽  
Deficient Mice ◽  
Necrosis Factor

In mice deficient in either lymphotoxin α (LT-α) or type I tumor necrosis factor receptor (TNFR-I), organized clusters of follicular dendritic cells (FDC) and germinal centers (GC) are absent from the spleen. We investigated the role of LT-α and TNFR-I in the establishment of spleen FDC and GC structure by using reciprocal bone marrow (BM) transfer. When LT-α–deficient mice were reconstituted with wild-type BM, FDC organization and the ability to form GC were restored, indicating that the LT-α–expressing cells required to establish organized FDC are derived from BM. The role of LT-α in establishing organized FDC structure was further investigated by the transfer of complement receptor 1 and 2 (CR1/2)–deficient BM cells into LT-α–deficient mice. Organized FDC were identified with both the FDC-M1 and anti-CR1 monoclonal antibodies in these BM-chimeric mice, indicating that these cells were derived from the LT-α–deficient recipient. Thus, expression of LT-α in the BM-derived cells, but not in the non–BM-derived cells, is required for the maturation of FDC from non-BM precursor cells. In contrast, when TNFR-I–deficient mice were reconstituted with wild-type BM, they showed no detectable FDC clusters or GC formation. This indicates that TNFR-I expression on non–BM-derived cellular components is necessary for the establishment of these lymphoid structures. TNFR-I–deficient BM was able to restore FDC organization and GC formation in LT-α–deficient mice, indicating that formation of these structures does not require TNFR-I expression on BM-derived cells. The data in this study demonstrate that FDC organization and GC formation are controlled by both LT-α–expressing BM-derived cells and by TNFR-I-expressing non–BM-derived cells.

Adenosine prevents phorbol ester injury in rabbit lungs: role of leukotrienes and TNF

1991 ◽  
Vol 71 (5) ◽  
pp. 1949-1955 ◽  
Author(s):  
J. D. Bradley ◽  
P. B. Zanaboni ◽  
R. O. Webster ◽  
L. J. Baudendistel ◽  
T. E. Dahms
Keyword(s):  
Lung Injury ◽  
Tumor Necrosis ◽  
Fold Increase ◽  
Blood Components ◽  
Myristate Acetate ◽  
Synthesis Inhibitor ◽  
Low Levels ◽  
Circulating Levels ◽  
Necrosis Factor

The objective of this study was to determine whether adenosine (ADO) prevents phorbol myristate acetate- (PMA) induced lung injury by modulating peptidoleukotrienes (LT) and/or tumor necrosis factor (TNF) production. PMA significantly increased pulmonary vascular resistance (PVR, 275 +/- 4 to 447 +/- 30 cmH2O.1–1.min) and microvascular filtration coefficient.(Kf, 0.024 +/- 0.002 to 0.040 +/- 0.006 g.min-1.cmH2O-1) in isolated blood-perfused rabbit lungs. ADO (5 mumol/min) blocked the increases in PVR (257 +/- 9 to 283 +/- 26) and Kf (0.028 +/- 0.005 to 0.018 +/- 0.002). After PMA (30 min), perfusate levels of LTC4 + LTD4 increased by 15.3 +/- 2.1 pg/ml; LTE4 increased by 15.1 +/- 4.1 pg/ml. ADO reduced the increase in LTC4 + LTD4 to 2.7 +/- 6.1 pg/ml, but total LT increased by 31.9 +/- 16.6 pg/ml, implying that ADO enhanced the conversion of LTC4 and LTD4 to LTE4. MK-886 (L663,536), an LT synthesis inhibitor, blocked the increase in total LT (6.1 +/- 13.9 pg/ml) but did not reduce the PMA-induced increase in Kf (0.022 +/- 0.003 to 0.035 +/- 0.005) or PVR (238 +/- 11 to 495 +/- 21). After PMA administration, perfusate TNF levels were not different from the 10-fold increase observed in control experiments and were not reduced by ADO or MK-886. TNF production was independent of perfusate blood components and presumably due to low levels of endotoxin in the perfusate (70–90 ng/ml). These results indicate that ADO does not protect against PMA-induced acute lung injury by altering circulating levels of LT or TNF.

A possible role of sphingosine in induction of apoptosis by tumor necrosis factor-α, in human neutrophils

FEBS Letters ◽  
1994 ◽  
Vol 355 (3) ◽  
pp. 267-270 ◽  
Author(s):  
Hideki Ohta ◽  
Yutaka Yatomi ◽  
Elizabeth A. Sweeney ◽  
Sen-itiroh Hakomori ◽  
Yasuyuki Igarashi
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Human Neutrophils ◽  
Induction Of Apoptosis ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals The role of tumor necrosis factor-α for interleukin-10 production by murine dendritic cells

2011 ◽  
Vol 266 (2) ◽  
pp. 165-171 ◽  
Author(s):  
Noriyuki Hirata ◽  
Yoshiki Yanagawa ◽  
Hisako Ogura ◽  
Masashi Satoh ◽  
Masayuki Noguchi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 10 ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals The Role of TRAIL/DRs in the Modulation of Immune Cells and Responses

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1469 ◽  
Author(s):  
Duygu Sag ◽  
Zeynep Ozge Ayyildiz ◽  
Sinem Gunalp ◽  
Gerhard Wingender
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Necrosis Factor ◽  
Immune Responses ◽  
Tumor Cells ◽  
Immune Cells ◽  
Tumor Necrosis ◽  
Death Receptors ◽  
Induction Of Apoptosis ◽  
Necrosis Factor

Expression of TRAIL (tumor necrosis factor–related apoptosis–inducing ligand) by immune cells can lead to the induction of apoptosis in tumor cells. However, it becomes increasingly clear that the interaction of TRAIL and its death receptors (DRs) can also directly impact immune cells and influence immune responses. Here, we review what is known about the role of TRAIL/DRs in immune cells and immune responses in general and in the tumor microenvironment in particular.

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